Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

/pdf/mds-clinical-diagnostic-criteria-for-parkinson-s-disease-74dzuucoq6.pdf

MDS clinical diagnostic criteria for Parkinson's disease

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

/pdf/a-randomized-trial-of-deep-brain-stimulation-for-parkinson-s-40jf18b006.pdf

A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease

Measuring Health: A Guide to Rating Scales and Questionnaires

The clinical diagnosis of Parkinson's disease rests on the identification of the characteristics related to dopamine deficiency that are a consequence of degeneration of the substantia nigra pars compacta. However, non-dopaminergic and non-motor symptoms are sometimes present before diagnosis and almost inevitably emerge with disease progression. Indeed, non-motor symptoms dominate the clinical picture of advanced Parkinson's disease and contribute to severe disability, impaired quality of life, and shortened life expectancy. By contrast with the dopaminergic symptoms of the disease, for which treatment is available, non-motor symptoms are often poorly recognised and inadequately treated. However, attention is now being focused on the recognition and quantitation of non-motor symptoms, which will form the basis of improved treatments. Some non-motor symptoms, including depression, constipation, pain, genitourinary problems, and sleep disorders, can be improved with available treatments. Other non-motor symptoms can be more refractory and need the introduction of novel non-dopaminergic drugs. Inevitably, the development of treatments that can slow or prevent the progression of Parkinson's disease and its multicentric neurodegeneration provides the best hope of curing non-motor symptoms.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(06)70373-8.pdf

Non-motor symptoms of Parkinson's disease: diagnosis and management

Ropinirole versus levodopa in Parkinson's disease.

Choreoathetoid movements are quite common in cerebral palsy (CP). This is the first report of a patient with choreoathetoid CP who was successfully treated with carbamazepine. Therefore, clinicians should try carbamazepine for involuntary movements in CP patients before pursuing other procudures.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mdc3.12002

Treatment of Involuntary Movements with Carbamazepine in Dystonic‐Choreoathetoid Cerebral Palsy

OBJECTIVE: : To determine if switching from (IR-TAC) to LCPT reduces TAC-associated tremor in kidney transplant recipients (KTR).
BACKGROUND: TAC-associated tremor is common and most evident at peak concentrations. Reduction or cessation of TAC reduces tremor but may increase the risk for transplant rejection. LCP-Tacro (Veloxis Pharmaceuticals) is a novel MeltDose formulation of TAC that is administered once-daily with reduced peak andcomparable exposure, allowing it to be administered at ~30% less than IR-TAC.
DESIGN/METHODS: We examined if converting stable IR-TAC patients who complain of tremor to LCPT results in improvement in hand tremor. Written informed consent was obtained from all subjects in this multicenter study. Tremor pre- and 7 days post-conversion was evaluated by independent, blinded neurologists using the Fahn-Tolosa-Marin (FTM) tremor rating scale and by accelerometry. The primary outcome measure was the change in the FTM total score. PGI-I (Patient Global Impression of Improvement) and the QUEST (Quality of Life in Essential Tremor) questionnaires were also obtained.
RESULTS: 38/44 subjects had evaluable pre- and post FTM scores. The mean (SD) absolute change in FTM was -5.35 ([7.50]; P P P <0.0005) and the QUEST also showed improvement (mean (SD) absolute change was -7.04 (9.41), mean percent change was -39.08% (39.43) (P< 0.001)).
CONCLUSIONS: : Results suggest IR-TAC-induced tremor may be ameliorated by switching to LCPT. The improvement in tremor appears clinically meaningful to neurologists based upon the FTM and accelerometry measurements and also meaningful to patients (PGI-I and QUEST).
Study Supported by: Veloxis Pharmaceuticals Disclosure: Dr. Morgan has received personal compensation for activities with Teva Neuroscience, Veloxis, Oakstone, UCB Pharma, and as an expert witness in litigation involving neurological issues. Dr. Morgan has received research support from National Institutes of Health and National Parkinson Foundation. Dr. Langone has nothing to disclose. Dr. Nigro has nothing to disclose. Dr. Sethi has received personal compensation for activities with Synosia and Veloxis, ADAMAS, Impax Laboratories and Teva Neuroscience as a consultant, and with Merz Pharmaceuticals as an employee. Dr. Sethi has received research support from GlaxoSmithKline Inc., Teva Neuroscience, Acadia, and Impax Laboratories.

Tacrolimus-Induced Tremor: Switching from Immediate-Release (IR-TAC) to LCP-Tacro Extended-Release Tacrolimus (LCPT) Reduces Tremor and Improves Quality of Life (P4.072)

Video #12. The caption on the footage reads: ‘‘Hysterical palsy of left arm with contracture. Extremely limited range of voluntary movements of fingers: attitudes of the hand maintained: peripheral segments move ‘‘en bloc.’’ Case #13. Hysteria. Hysterical tremor at rest and in action, simulating action tremor of organic origin. Case #12. The brief video shows a patient with wrist flexion and elbow flexion with no movements distally. It is difficult to see any trophic changes on the video. Wilson was well aware of the vasomotor changes seen in hysteria, at least some of which were caused by immobility. These trophic changes are seen today in the disorder variously known as causalgiadystonia syndrome or the syndrome of fixed dystonia after peripheral injury. The current thinking is that in a majority of cases the etiology of peripheral dystonia after minor trauma is psychogenic. Wilson uses the term contracture in the caption but it is unclear if this was a true contracture as demonstrated by an absence of muscle activity on electromyography and persistence of abnormal posture during anesthesia. The latter was well described by Gowers, who described that in hysteria ‘‘spasmodic contractures’’ can persist even during sleep and relax only with chloroform narcosis and if continued over years can lead to permanent contractures that are no longer responsive to chloroform. Wilson was well aware of hysteria with its protean manifestations. However, he used the word neuroses differently than it is currently used. He stated that ‘‘the current neurological opinion takes the word neurosis to signify a disorder of nervous function for which as yet no underlying basis has been found.’’ He disliked the use of the term neurosis by some contemporaries to describe mental disorders with somatic manifestations. He derided the distinction between organic and functional disease states. He stated that ‘‘symptoms stand for either excitation or arrest of function or exhibit a sequence in which the latter follows the first. Without exception all are functional.’’ The terminology used to describe cases #12 and #13 has evolved over time but no single label satisfies everyone even today. However, most would employ the word psychogenic to describe these cases. It is apparent that he had given a lot of thought to the mechanisms by which hysteria results in neurological signs and symptoms. In a 1931 paper that is worth quoting: ‘‘I believe we must depend on the objective signs of hysterical disease if we are to progress towards its unification. Now the chief point, as it seems to me, on which more light is wanted, is the mechanism of production of the symptoms. Granted that a particular mental state is accountable for the disturbances of function, how are these actually brought into being?’’ He wondered why in some cases hysteria causes tremor and in other cases, paralysis. He goes on to state that ‘‘there is a block somewhere, a pure inhibition, in the case of negative symptoms or, on the other hand, inhibition is removed and releasephenomena come into being as positive symptoms. It seems logically sound to seek to interpret cortical activities in physiological terms alone, and to avoid use of the psychological term ‘volition’ altogether. Admitting that many of the phenomena of hysteria belong obviously to the highest grade of activity, are so like ‘volitional’ actions as to be thought indicative of deception or simulation.’’ Brain mechanisms underlying hysterical conversion symptoms are still poorly known. Recent functional magnetic resonance imaging (fMRI) studies have revealed that the motor intention is preserved as evidenced by an activation of the right motor cortex despite left paralysis. However, there are concomitant increases in ventromedial prefrontal cortex (vmPFC) regions that normally mediate motivational and affective processing. Single photon emission computerized tomography using (99m)Tc–ethylcysteinate dimer (ECD) reveals a decrease of regional cerebral blood flow in the -----------------------------------------------------------*Correspondence to: Dr. Kapil D. Sethi, Movement Disorders Program, Department of Neurology, Georgia Health Sciences University, 1429 Harper Street, HF-1121A, Augusta, GA 30912; ksethi@georgiahealth.edu Relevant conflicts of interest/financial disclosures: The author has no conflicts of interest to report. Full financial disclosures and author roles may be found in the online version of this article.

The Wilson films — Psychogenic

A 62-year-old woman with 12-year history of Parkinson’s disease (PD) developed intermittent severe neck flexion, associated with pain. Anterocollis was one of the initial symptoms noted by the patient at the age of 50. Examination while off levodopa showed severe anterocollis, generalized bradykinesia, and gait difficulty. There was no associated neck muscle weakness, dysautonomic symptoms, or pseudohypertrophy of her muscles. Her head stayed up even when she was lying down. She was on carbidopa/levodopa 25/100 (2 tabs q2 hours) and carbidopa/levodopa 50/200 controlled-release (1 tab at bedtime); her anterocollis and neck pain improved dramatically with levodopa (Video S1). The anterocollis resolved after bilateral subthalamic deep brain stimulation (STN DBS). STN was chosen as off symptoms respond better with this target. Anterocollis has been defined as marked (minimum 45°) neck flexion (maybe partially overcome by voluntary or passive movement), unable to fully extend the neck against gravity but able to exert force against the resistance of the examiner’s hand. Dropped head syndrome is associated with neurodegenerative diseases (PD, multiple system atrophy [MSA], dementia with Lewy bodies, progressive supranuclear palsy [PSP], dystonias [dopa-responsive dystonia or segmental dystonia], motor neuron disease, inherited or acquired myopathies, myasthenia gravis, and drugs [dopamine-agonists, amantadine, donepezil]). Anterocollis is common in MSA with a prevalence rate of 42%, whereas the prevalence in PD is 5.8% and it is difficult to manage. In these cases, anterocollis was constantly present and did not respond to levodopa. Anterocollis tends to occur in MSA slightly earlier than PD. The cause of anterocollis in Parkinsonism can be dystonia of cervical flexors, myopathy of cervical extensors, or both. Some patients with head drop in PD may improve with an increase in the dose of antiparkinsonian drugs, but anterocollis only in the “off” state has not been reported. Anterocollis is not exclusive to Parkinsonism and our case demonstrates anterocollis as an “off” phenomenon in PD. The possible pathophysiology of anterocollis in our case is presumed to be “off” dystonia, as there was no associated muscle weakness.

Kapil D. Sethi

Papers

Ropinirole versus levodopa in Parkinson's disease.

Treatment of Involuntary Movements with Carbamazepine in Dystonic‐Choreoathetoid Cerebral Palsy

Tacrolimus-Induced Tremor: Switching from Immediate-Release (IR-TAC) to LCP-Tacro Extended-Release Tacrolimus (LCPT) Reduces Tremor and Improves Quality of Life (P4.072)

The Wilson films — Psychogenic

Anterocollis as an "Off" Phenomenon in Parkinson Disease.