Whole Clinic Research Enrollment in Parkinson's Disease: The Molecular Integration in Neurological Diagnosis (MIND) Study.

BACKGROUND: Observational studies in Parkinson's disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. OBJECTIVE: To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. METHODS: All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. RESULTS: Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). CONCLUSIONS: We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization.

Psychogenic (Functional) Movement Disorders.

PURPOSE OF REVIEW: This article reviews a practical approach to psychogenic movement disorders to help neurologists identify and manage this complex group of disorders. RECENT FINDINGS: Psychogenic movement disorders, also referred to as functional movement disorders, describe a group of disorders that includes tremor, dystonia, myoclonus, parkinsonism, speech and gait disturbances, and other movement disorders that are incongruent with patterns of pathophysiologic (organic) disease. The diagnosis is based on positive clinical features that include variability, inconsistency, suggestibility, distractibility, suppressibility, and other supporting information. While psychogenic movement disorders are often associated with psychological and physical stressors, the underlying pathophysiology is not fully understood. Although insight-oriented behavioral and pharmacologic therapies are helpful, a multidisciplinary approach led by a neurologist, but also including psychiatrists and physical, occupational, and speech therapists, is needed for optimal outcomes. SUMMARY: The diagnosis of psychogenic movement disorders is based on clinical features identified on neurologic examination, and neurophysiologic and imaging studies can provide supporting information.

Recent Advances in Understanding and Managing Tourette Syndrome.

Tourette syndrome (TS) is a neurologic and behavioral disorder consisting of motor and phonic tics with onset in childhood or adolescence. The severity of tics can range from barely perceptible to severely impairing due to social embarrassment, discomfort, self-injury, and interference with daily functioning and school or work performance. In addition to tics, most patients with TS have a variety of behavioral comorbidities, including attention deficit hyperactivity disorder and obsessive-compulsive disorder. Studies evaluating the pathophysiology of tics have pointed towards dysfunction of the cortico-striato-thalamo-cortical circuit, but the mechanism of this hyperkinetic movement disorder is not well understood. Treatment of TS is multidisciplinary, typically involving behavioral therapy, oral medications, and botulinum toxin injections. Deep brain stimulation may be considered for "malignant" TS that is refractory to conventional therapy. In this review, we will highlight recent developments in the understanding and management strategies of TS.

The relationship between essential tremor and Parkinson's disease.

Essential tremor (ET) and Parkinson's disease (PD) are the two most common tremor disorders encountered in a movement disorders clinic. Although distinct clinical-pathological entities, both disorders may share overlapping features in addition to rest and postural tremor, such as bradykinesia, rigidity, gait and balance impairment and some non-motor signs. A subset of patients may have a combination of long-standing ET with subsequent PD (ET-PD). There are several lines of evidence from clinical, epidemiologic, imaging, genetic and pathologic studies supporting a link between ET and PD, greater than by chance alone. In this review we will discuss the latest data supporting a relationship between ET and PD and the implications for possible pathogenic link and treatment.

Psychogenic movement disorders.

Psychogenic movement disorders (PMDs) can present with varied phenomenology that may resemble organic movement disorders. The diagnosis is based on clinical evaluation with a supporting history and classic features on neurologic examination. Ancillary testing, such as imaging and neurophysiologic studies, can provide supplementary information but is not necessary for diagnosis. There is no standard protocol for the treatment of PMDs, but a multidisciplinary approach has been recommended. This review discusses the clinical characteristics of various PMDs as well as ancillary testing, treatment, and research in the pathophysiology of this complex group of disorders.

Psychogenic tremor: a video guide to its distinguishing features.

BACKGROUND: Psychogenic tremor is the most common psychogenic movement disorder. It has characteristic clinical features that can help distinguish it from other tremor disorders. There is no diagnostic gold standard and the diagnosis is based primarily on clinical history and examination. Despite proposed diagnostic criteria, the diagnosis of psychogenic tremor can be challenging. While there are numerous studies evaluating psychogenic tremor in the literature, there are no publications that provide a video/visual guide that demonstrate the clinical characteristics of psychogenic tremor. Educating clinicians about psychogenic tremor will hopefully lead to earlier diagnosis and treatment. METHODS: We selected videos from the database at the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine that illustrate classic findings supporting the diagnosis of psychogenic tremor. RESULTS: We include 10 clinical vignettes with accompanying videos that highlight characteristic clinical signs of psychogenic tremor including distractibility, variability, entrainability, suggestibility, and coherence. DISCUSSION: Psychogenic tremor should be considered in the differential diagnosis of patients presenting with tremor, particularly if it is of abrupt onset, intermittent, variable and not congruous with organic tremor. The diagnosis of psychogenic tremor, however, should not be simply based on exclusion of organic tremor, such as essential, parkinsonian, or cerebellar tremor, but on positive criteria demonstrating characteristic features. Early recognition and management are critical for good long-term outcome.

Parkinson disease subtypes.

IMPORTANCE: It is increasingly evident that Parkinson disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. OBJECTIVE: To evaluate available evidence, based on findings from clinical, imaging, genetic and pathologic studies, supporting the differentiation of PD into subtypes. EVIDENCE REVIEW: We performed a systematic review of articles cited in PubMed between 1980 and 2013 using the following search terms: Parkinson disease, parkinsonism, tremor, postural instability and gait difficulty, and Parkinson disease subtypes. The final reference list was generated on the basis of originality and relevance to the broad scope of this review. FINDINGS: Several subtypes, such as tremor-dominant PD and postural instability gait difficulty form of PD, have been found to cluster together. Other subtypes also have been identified, but validation by subtype-specific biomarkers is still lacking. CONCLUSIONS AND RELEVANCE: Several PD subtypes have been identified, but the pathogenic mechanisms underlying the observed clinicopathologic heterogeneity in PD are still not well understood. Further research into subtype-specific diagnostic and prognostic biomarkers may provide insights into mechanisms of neurodegeneration and improve epidemiologic and therapeutic clinical trial designs.

Treatment of dystonia.

Selecting the appropriate treatment for dystonia begins with proper classification of disease based on age, distribution, and underlying etiology. The therapies available for dystonia include oral medications, botulinum toxin, and surgical procedures. Oral medications are generally reserved for generalized and segmental dystonia. Botulinum toxin revolutionized the treatment of focal dystonia when it was introduced for therapeutic purposes in the 1980s. Surgical procedures are available for medication-refractory dystonia, markedly affecting an individual's quality of life.

Botulinum toxin for the treatment of movement disorders.

After botulinum toxin was initially used to treat strabismus in the 1970s, others started using it to treat movement disorders including blepharospasm, hemifacial spasm, cervical dystonia, spasmodic dysphonia, and oromandibular dystonia. It was discovered that botulinum toxin can be an effective treatment for focal movement disorders with limited side effects. Over the past three decades, various formulations of botulinum toxin have been developed and the therapeutic use of these toxins has expanded in movement disorders and beyond. We review the history and mechanism of action of botulinum toxin, as well as describe different formulations available and their potential therapeutic uses in movement disorders.

Personality profile in essential tremor: a case-control study.

BACKGROUND: Neuropsychiatric findings described in essential tremor (ET) include depression and anxiety. There may be personality features as well; in 2004, we demonstrated higher harm avoidance (HA) scores in ET patients than controls. We now (1) determined whether this finding could be replicated in a new sample of cases and controls, and (2) analyzed HA sub-scores (HA1-HA4) to further understand case-control differences. DESIGN/METHODS: 60 ET cases and 35 controls were evaluated using the Tridimensional Personality Questionnaire (TPQ), which assesses three domains of personality: HA, novelty seeking (NS), and reward dependence (RD). RESULTS: Total HA and total NS scores were marginally higher in cases than controls (14.8 ± 7.6 vs. 12.4 ± 5.3, p = 0.09) and (13.8 ± 5.4 vs. 11.8 ± 4.9, p = 0.09), respectively. When adjusted for age and gender, cases and controls differed with respect to total HA score (p = 0.03) but not total NS score (p = 0.10). Further analysis of HA sub-scores demonstrated that HA1 (anticipatory worry and pessimism) and HA4 (fatigability and asthenia) were most robustly elevated in cases vs. controls (p = 0.04 and p = 0.01, respectively). CONCLUSIONS: This study suggests that ET cases have a personality profile characterized by a greater HA, with certain domains of HA most affected. It is unclear whether this personality profile is pre-morbid or is a co-morbid feature of the illness, nor it is known whether the greater tendency towards HA in ET lessens receptivity to deep brain stimulation surgery and other therapies.

Distinguishing essential tremor from Parkinson's disease: bedside tests and laboratory evaluations.

Distinguishing essential tremor from Parkinson's disease can be challenging, both in the early stages of these diseases and as these diseases progress. Various tremor types (rest, postural, kinetic and intention) may be seen in both essential tremor and Parkinson's disease. Furthermore, with time, the two diseases may coexist within a single patient. Detailed clinical examination with attention to specific features of tremor (frequency, amplitude, pattern and distribution) and associated neurological findings may help distinguish patients with the two diseases. Laboratory testing may provide information that further aids in differentiating the two diseases. These tests include accelerometry and surface electromyography, spiral analysis, dopamine transporter imaging, olfactory testing and, eventually, postmortem histopathology. These tests have limitations and their diagnostic utility requires additional study.

Treatment options for sleep dysfunction in Parkinson's disease.

OPINION STATEMENT: Sleep disturbance is an important feature of Parkinson's disease (PD) that deserves clinical attention. Various disorders need to be considered and treatment should be customized to the patient's specific symptoms and lifestyle. Evaluation of a PD patient complaining of difficulty sleeping begins with a detailed history from the patient and bed partner about the specific problem the patient is experiencing. It is important to inquire about difficulties with sleep onset, frequent awakenings, increased movements during sleep, acting out dreams, uncomfortable motor symptoms, disordered breathing, and nocturia. Current medications should be reviewed to determine whether the recent addition of a drug or a change in dose may be contributing to sleep difficulties, and one should ask about daytime sleepiness, frequent daytime naps, and sleep hygiene in the evening that can contribute to problems sleeping at night. The goal of therapy is to restore quality nighttime sleep without excessive daytime sedation and to improve the patient's daily mental and physical function and overall quality of life.

A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal function and cardiovascular risk factors in kidney transplant recipients.

BACKGROUND: There are few data directly comparing the effects of two-hour postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0-Tac) on renal function and cardiovascular risk factors. METHODS: We studied 378 (202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto, Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of diet in renal disease four-variable equation), mean arterial pressure (MAP), total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months posttransplant. The independent effect of treatment/monitoring strategies on continuous outcomes and time-to-NODM was modeled using linear and Cox regression, respectively. RESULTS: Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6 vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2-CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64 ml/min between months one and six posttransplant. There was no significant difference in average MAP and TC. In a stepwise multivariable Cox model and a propensity score analysis, there was no significant association between the type of treatment/monitoring strategy and time-to-NODM. CONCLUSIONS: There was a greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six months posttransplant. However, MAP, TC, and the risk of NODM were comparable in both treatment/monitoring groups. The long-term impact of short-term reductions in eGFR as a function of the type of treatment/monitoring strategy requires further study.