Researchers have consistently observed in right-handed individuals across normal and disease states that the ‘dominant’ left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson’s disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right ‘composite scores’, were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
While DBS on the ‘dominant’ left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
Unilateral DBS; STN; GPi; Parkinson’s disease; UPDRS
Research in movement disorders in 2012 had led to advances in understanding the pathogenic mechanisms of disease and to development of potential novel therapeutic approaches. Key advances include elucidating mechanisms of spreading neurodegenerative pathology, immunotherapy, stem cells, genetics and deep brain stimulation in Parkinsonisms and related disorders.
Candidacy for deep brain stimulation (DBS) in Parkinson disease (PD) is typically assessed by the preoperative motor response to levodopa along with an interdisciplinary evaluation. However, recent cases treated at our institution have achieved good outcomes with DBS despite a sub-30% improvement in motor scores. The aim of this study was to examine the outcomes of DBS in a subset of patients who failed to reach the 30% motor improvement threshold.
A review of all DBS patients treated at the University of Florida Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS database. All patients with sub-30% improvement in Unified Parkinson Disease Rating Scale Part III after dopaminergic medication administration were included.
Nine patients were identified; DBS was performed for severe dyskinesia (n = 5), “on/off motor” fluctuations (n = 1) and medication-refractory tremor (n = 3). The target symptoms were improved in all patients. Postoperatively, scores on the Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson disease questionnaire-39 improved (P < 0.05).
Although motor response to levodopa remains the primary selection criteria for DBS candidacy in Parkinson disease, patients who do not meet the 30% threshold and have disabling symptoms may still benefit from DBS. Select patients with severe dyskinesia, “on/off” motor fluctuations, and/or medication-refractory tremor may experience significant benefits from DBS and should be considered on a case by case basis through an interdisciplinary team evaluation.
deep brain stimulation; Parkinson disease; levodopa challenge test; dyskinesia; on-off motor fluctuations; tremor; quality of life
The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies.
DBS; Dysphagia; Swallow; Aspiration pneumonia; Parkinson’s disease; Review
The purpose of this study was to determine if individuals with Parkinson’s disease (PD) demonstrate abnormal respiratory events when swallowing thin liquids. In addition, this study sought to define associations between respiratory events, swallowing apnea duration, and penetration–aspiration (P–A) scale scores. Thirty-nine individuals with PD were administered ten trials of a 5-ml thin liquid bolus. P–A scale score quantified the presence of penetration and aspiration during the swallowing of a 3-oz sequential bolus. Participants were divided into two groups based on swallowing safety judged during the 3-oz sequential swallowing: Group 1 = P–A ≤ 2; Group 2 = P–A ≥ 3. Swallows were examined using videofluoroscopy coupled with a nasal cannula to record respiratory signals during the event(s). Findings indicated that expiration was the predominant respiratory event before and after swallowing apnea. The data revealed no differences in our cohort versus the percentages of post-swallowing events reported in the literature for healthy adults. In addition, individuals with decreased swallowing safety, as measured by the P–A scale, were more likely to inspire after swallows and to have shorter swallowing apnea duration. Individuals who inspired before swallow also had longer swallowing apnea duration. The occurrence of inspiratory events after a swallow and the occurrence of shorter swallowing apnea durations may serve as important indicators during clinical swallowing assessments in patients at risk for penetration or aspiration with PD.
Dysphagia; Penetration–aspiration; Inspiration; Expiration; Parkinson’s disease; Deglutition; Deglutition disorders
Apathy is a common neuropsychiatric feature of Parkinson’s disease (PD), but little is known of relationships between apathy and specific medications in PD. Following a retrospective database and chart review of 181 Parkinson’s patients, relationships between Apathy Scale scores and use of psychotropic and antiparkinsonian medications were examined with multiple regression. Controlling for age, sex, education, and depression, the use of selective serotonin reuptake inhibitors (SSRIs), but not other antidepressants, was associated with greater apathy. Use of monoamine oxidase B inhibitors was associated with less apathy. Longitudinal studies are needed to evaluate a potential SSRI-induced apathy syndrome in PD.
Depression is a clinically heterogeneous disorder common in Parkinson disease (PD). The goal of this study was to characterize PD depression in terms of components, including negative affect, apathy, and anhedonia. Ninety-five, nondemented individuals with idiopathic PD underwent a diagnostic interview and psychological battery. Twenty-seven patients (28%) met Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM-IV]) criteria for a current depressive episode. The best-fitting confirmatory factor analysis model had 3 factors (negative affect, apathy, and anhedonia). Apathy loaded most strongly onto a second-order factor representing global psychological disturbance. All factors are uniquely associated with depression status. Negative affect exhibited the strongest relationship. Psychological disturbance in PD is heterogeneous and can produce symptoms of apathy, anhedonia, and negative affect. Apathy appears to be the core neuropsychiatric feature of PD, whereas negative affect (eg, dysphoria) seems to be most pathognomonic of depression. Future studies should examine the specific neural correlates and treatment response patterns unique to these 3 components.
apathy; anhedonia; negative affect; dysphoria; anxiety; confirmatory factor analysis
Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinson's disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research.
Deep brain stimulation; Frequency; Non-regular; Temporal pattern
Background. Movement disorders fellowships are an important source of future clinician-specialists and clinician-scientists for the field. Scant published information exists on the number and characteristics of North American movement disorders fellowship training programs.
Methods. A 31-item internet-based survey was formulated and distributed to academic movement disorders listed in the American Academy of Neurology (AAN) directory as having a movement disorders fellowship and to all National Parkinson Foundation Centers of Excellence and Care Centers in North America.
Results. There was a 77% response rate among academic movement disorders centers. Broad similarities in clinical training were identified. The two most important rated missions of maintaining a movement disorders fellowship were contributions to scholarly activities and to fulfilling a critical need for specialists. Almost a quarter of fellowship programs did not offer a fellowship slot during the most recent academic year. Fellowship directors cited a wide variety of funding sources, but their top concern was lack of available funding for fellowship programs.
Conclusions. North American movement disorders fellowship training programs currently offer similar methods of clinical training and education. Lack of funding was the most important obstacle to maintaining fellowship programs and should be made a priority for discussion in the field.
Dystonia is a movement disorder characterized by involuntary sustained muscle contractions causing twisting and repetitive movements or abnormal postures. Some cases of primary and neurodegenerative dystonia have been associated with mutations in individual genes critical to the G1-S checkpoint pathway (THAP1, ATM, CIZ1 and TAF1). Secondary dystonia is also a relatively common clinical sign in many neurogenetic disorders. However, the contribution of structural variation in the genome to the etiopathogenesis of dystonia remains largely unexplored.
Cytogenetic analyses with the Affymetrix Genome-Wide Human SNP Array 6.0 identified a chromosome 13q34 duplication in a 36 year-old female with global developmental delay, facial dysmorphism, tall stature, breast cancer and dystonia, and her neurologically-normal father. Dystonia improved with bilateral globus pallidus interna (GPi) deep brain stimulation (DBS). Genomic breakpoint analysis, quantitative PCR (qPCR) and leukocyte gene expression were used to characterize the structural variant. The 218,345 bp duplication was found to include ADPRHL1, DCUN1D2, and TMCO3, and a 69 bp fragment from a long terminal repeat (LTR) located within Intron 3 of TFDP1. The 3' breakpoint was located within Exon 1 of a TFDP1 long non-coding RNA (NR_026580.1). In the affected subject and her father, gene expression was higher for all three genes located within the duplication. However, in comparison to her father, mother and neurologically-normal controls, the affected subject also showed marked overexpression (2×) of the transcription factor TFDP1 (NM_007111.4). Whole-exome sequencing identified an SGCE variant (c.1295G > A, p.Ser432His) that could possibly have contributed to the development of dystonia in the proband. No pathogenic mutations were identified in BRCA1 or BRCA2.
Overexpression of TFDP1 has been associated with breast cancer and may also be linked to the tall stature, dysmorphism and dystonia seen in our patient.
Dystonia; Chromosome 13q34; Duplication; TFDP1; Breast cancer; G1-S Checkpoint pathway
The success of cellular therapies for Parkinson’s disease (PD) will depend not only a conducive growth environment in vivo, but also on the ex vivo amplification and targeted neural differentiation of stem/progenitor cells. Here, we demonstrate the in vitro proliferative and differentiation potential of stem/progenitor cells, adult human neural progenitor cells (“AHNPs”) isolated from idiopathic PD postmortem tissue samples and, to a lesser extent, discarded deep brain stimulation electrodes. We demonstrate that these AHNPs can be isolated from numerous structures (e.g. substantia nigra, “SN”) and are able to differentiate into both glia and neurons, but only under particular growth conditions including co-culturing with embryonic stem cell-derived neural precursors; this suggests that PD multipotent neural stem/progenitor cells do reside with the SN and other areas, but by themselves appear to lack key factors required for neural differentiation. AHNPs engraft following ex vivo expansion and transplantation into the rodent brain, demonstrating their regenerative potential. Our data demonstrate the presence and capacity of endogenous stem/progenitor cells in the PD brain.
Parkinson’s disease; neurogenesis; neural stem cell; neural progenitor cell; cell culture
In 1961, David C. Poskanzer and Robert S. Schwab presented a paper, “Studies in the epidemiology of Parkinson's disease predicting its disappearance as a major clinical entity by 1980.” This paper introduced the hypothesis that Parkinson's disease was derived from a single aetiology, the influenza virus. We review the original Poskanzer and Schwab hypothesis that Parkinson's disease was based on the association between the 1918-19 influenza epidemic and the later observation of Parkinsonism in some influenza sufferers. We also further explore the prediction that Parkinson's disease would totally disappear as an entity once original influenza victims were all deceased. Current research has revealed that there are many potential causes and factors important in the occurrence of Parkinson's disease, postencephalitic Parkinsonism, and encephalitis lethargica. Poskanzer and Schwab presented a novel hypothesis; however, it was proven false by a combination of research and time.
Cortical circuits encode sensory stimuli through the firing of neuronal ensembles, and also produce spontaneous population patterns in the absence of sensory drive. This population activity is often characterized experimentally by the distribution of multineuron “words” (binary firing vectors), and a match between spontaneous and evoked word distributions has been suggested to reflect learning of a probabilistic model of the sensory world. We analyzed multineuron word distributions in sensory cortex of anesthetized rats and cats, and found that they are dominated by fluctuations in population firing rate rather than precise interactions between individual units. Furthermore, cortical word distributions change when brain state shifts, and similar behavior is seen in simulated networks with fixed, random connectivity. Our results suggest that similarity or dissimilarity in multineuron word distributions could primarily reflect similarity or dissimilarity in population firing rate dynamics, and not necessarily the precise interactions between neurons that would indicate learning of sensory features.
Non-motor symptoms are increasingly recognized as important determinants of quality of life and disability in a wide range of movement disorders. There is a limited body of research suggesting that many of these symptoms are also commonly associated with primary and other genetic forms of dystonia. However, the significance, etiology, pathophysiology, and treatment of these symptoms remains poorly described. The following is a review of the literature which focuses primarily on the association of these types of dystonia with psychiatric disorders, cognition, sleep, pain, and autonomic symptoms. We will also discuss potential mechanisms and approaches to treatment for non-motor features of dystonia.
dystonia; non-motor; depression; anxiety; cognition; pain; sleep
Few studies exist in the literature investigating the impact of idiopathic Parkinson’s Disease (IPD) on swallow-related quality of life. We therefore aimed in this project to: (1) evaluate swallow-specific quality of life in IPD; (2) delineate potential relationships between IPD duration and severity with swallow-specific quality of life; (3) investigate relationships between swallow-specific quality of life and general health-related quality of life; and (4) investigate relationships between swallow-specific quality of life and depression. Thirty-six patients diagnosed with IPD with and without dysphagia filled out self-report assessments of the SWAL-QOL, Parkinson’s Disease Questionnaire-39 (PDQ-39), and Beck Depression Inventory (BDI). A series of Mann Whitney U tests were performed between non-dysphagic and dysphagic groups for the total SWAL-QOL score and the 10 SWAL-QOL domains. Spearman’s Rho correlation analyses were performed between the SWAL-QOL and (1) PDQ-39; (2) Hoehn and Yahr stage; (3) PD disease duration; (4) UPDRS “on” score; and (5) the BDI. The dysphagia swallowing group reported significant reductions compared to the nondysphagic group for the total SWAL-QOL score (P = 0.02), mental health domain score (P = 0.002) and social domain score (P = 0.002). No relationships existed between swallow-specific quality of life and disease duration or severity. Significant relationships existed between swallow-specific quality of life and general health-related quality of life (rs =−0.56, P = 0.000) and depression (rs = −0.48, P = 0.003). These exploratory data highlight the psychosocial sequelae that swallowing impairment can have in those with IPD and suggest a possible association between swallowing, social function, and depression.
swallowing; idiopathic Parkinson’s disease; quality of life; depression
The psychological pressure on soldiers during World War I (WWI) and other military conflicts has resulted in many reported cases of psychogenic gait as well as other movement disorders. In this paper, psychogenic movement disorders captured in the WWI film footage “War Neuroses” is reanalyzed.
Two movement disorders specialists re-examined film images of 21 WWI patients with various and presumed psychogenic manifestations, pre- and post treatment. The film was recorded by Arthur Hurst, a general physician with an interest in neurology.
All 21 subjects were males, and all presented with symptoms relating to war trauma or a psychological stressor (e.g., being buried, shrapnel wounds, concussion, or trench fever). The most common presenting feature was a gait disorder, either pure or mixed with another movement disorder (15), followed by retrograde amnesia (2), abnormal postures (pure dystonia) (1), facial spasm (1), head tremor (1), “hyperthyroidism-hyperadrenalism” (1). Nineteen patients received treatment, and the treatment was identified in nine cases. In most cases, treatment was short and patients improved almost immediately. Occupational therapy was the most common treatment. Other effective methods were hypnosis (1), relaxation (1), passive movements (2), and probable “persuasion and re-education” (6).
The high success rate in treating psychogenic disorders in Hurst’s film would be considered impressive by modern standards, and has raised doubt in recent years as to whether parts of the film were staged and/or acted.
Psychogenic movement disorders; Arthur Hurst; shell shock; psychogenic gait; World War I
To evaluate the relationship between knee extensor strength, postural stability, functional ambulation, and disease severity in Parkinson’s disease (PD).
A cohort study.
University research laboratory.
Patients (N = 44) with idiopathic PD.
Main Outcome Measures
Participants were evaluated on their isokinetic knee extensor strength. Additionally, participants completed an assessment of their postural stability (Functional Reach Test for static stability and a dynamic postural stability assessment as measured by the center of pressure–center of mass moment arm during gait initiation). Participants also underwent an evaluation of their functional ambulation as measured by a 6-minute walk test. Lastly, participants were evaluated by a neurologist specially trained in movement disorders to assess neurologic status and disease severity using the Unified Parkinson’s Disease Rating Scale and the Hoehn and Yahr disability score.
Knee extensor strength positively correlated with dynamic postural stability and negatively correlated with disease severity. Further, dynamic postural stability was negatively correlated to disease severity and positively correlated with functional ambulation in this cohort of patients with PD (P < .05). The results also suggest that the Functional Reach Test may be a valuable assessment tool to examine postural stability in PD.
These findings suggest a malleable relationship between knee extensor strength, dynamic stability, and disease severity in PD. Although strength is only one piece of the puzzle in the functional outcome of PD, these findings may assist clinicians in designing appropriate interventions aimed at increasing function and decreasing fall risk in PD.
Movement disorders; Neurodegenerative diseases; Rehabilitation
Deep brain stimulation (DBS) has been associated with mood sequelae in a subset of patients operated on in either the subthalamic nucleus or the globus pallidus internus for the treatment of Parkinson disease.
To compare mood and motor outcomes in those with and without a presurgical history of depression.
Unilateral subthalamic nucleus or unilateral globus pallidus internus DBS patients followed up for a minimum of 6 months were included. All patients underwent a comprehensive outpatient psychiatric evaluation by a board-certified psychiatrist. Psychiatric diagnoses were based on Diagnostic and Statistical Manual, fourth edition, text revision, nomenclature (American Psychiatric Association, 2000). Motor and mood outcomes were compared.
A total of 110 patients were included. There were no significant differences in baseline variables between the 2 groups. Those with a preoperative history of depression had significantly higher Beck Depression Inventory scores than the nondepression group after DBS (8.97 ± 7.55 vs 5.92 ± 5.71; P = .04). Patients with a depression history had less improvement (11.6%) in pre/post-DBS change when Unified Parkinson Disease Rating Scale motor scores were compared (P = .03) after adjustment for stimulation site and baseline demographic and clinical variables. Patients with a higher levodopa equivalent dose had a worse clinical motor outcome.
Patients with a preoperative depression history had higher Beck Depression Inventory scores after DBS and significantly less (albeit small) improvement in pre/post-DBS change in Unified Parkinson Disease Rating Scale motor scores than patients without a history of depression.
DBS; Deep brain stimulation; Depression; DSM; Outcomes; Psychiatry; Psychology
We aimed in this investigation to study deep brain stimulation (DBS) battery drain with special attention directed toward patient symptoms prior to and following battery replacement.
Previously our group developed web-based calculators and smart phone applications to estimate DBS battery life (http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator).
A cohort of 320 patients undergoing DBS battery replacement from 2002–2012 were included in an IRB approved study. Statistical analysis was performed using SPSS 20.0 (IBM, Armonk, NY).
The mean charge density for treatment of Parkinson’s disease was 7.2 µC/cm2/phase (SD = 3.82), for dystonia was 17.5 µC/cm2/phase (SD = 8.53), for essential tremor was 8.3 µC/cm2/phase (SD = 4.85), and for OCD was 18.0 µC/cm2/phase (SD = 4.35). There was a significant relationship between charge density and battery life (r = −.59, p<.001), as well as total power and battery life (r = −.64, p<.001). The UF estimator (r = .67, p<.001) and the Medtronic helpline (r = .74, p<.001) predictions of battery life were significantly positively associated with actual battery life. Battery status indicators on Soletra and Kinetra were poor predictors of battery life. In 38 cases, the symptoms improved following a battery change, suggesting that the neurostimulator was likely responsible for symptom worsening. For these cases, both the UF estimator and the Medtronic helpline were significantly correlated with battery life (r = .65 and r = .70, respectively, both p<.001).
Battery estimations, charge density, total power and clinical symptoms were important factors. The observation of clinical worsening that was rescued following neurostimulator replacement reinforces the notion that changes in clinical symptoms can be associated with battery drain.
Deep brain stimulation is a treatment for select cases of medication refractory movement disorders including Parkinson’s disease. Deep brain stimulation has not been recommended for treatment in multiple system atrophy patients. However, the paucity of literature documenting the effects of deep brain stimulation in multiple system atrophy patients and the revelation of a levodopa-responsive subtype of multiple system atrophy suggests further investigation is necessary.
This study summarizes the positive and negative effects of deep brain stimulation treatment in two pathologically confirmed multiple system atrophy patients from the University of Florida Deep Brain Stimulation-Brain Tissue Network. Clinical diagnosis for the two patient cases did not match the neuropathological diagnosis. We noted that in both pathologically confirmed multiple system atrophy patients, death occurred as a result of myocardial infarction. Importantly, there was reported transient benefit in levodopa responsive features that indicate deep brain stimulation may be an option for select multiple system atrophy patients.
Deep Brain Stimulation; Pathology; Multiple System Atrophy
Apathy is a common feature of Parkinson's disease (PD) that can manifest independently of depression, but little is known about its natural progression in medically-managed patients. The present study sought to characterize and compare trajectories of apathy, depression, and motor symptoms in PD over 18 months.
Data from a sample of 186 PD patients (mean disease duration of 8.2 years) followed by the University of Florida Movement Disorders Center were obtained from a clinical research database. Scores on the Unified Parkinson's Disease Rating Scale (motor portion), Apathy Scale, and Beck Depression Inventory at three time-points (baseline, 6 months, 18 months) were analyzed in a structural equation modeling framework.
A multivariate growth model controlling for age, sex, education, and disease duration identified linear worsening of both apathy (slope estimate = 0.73; p <.001) and motor symptoms (slope estimate = 1.51; p <.001), and quadratic changes in depression (slope estimate = 1.18; p = .07). All symptoms were positively correlated. Higher education was associated with lower apathy, depression, and motor severity. Advanced age was associated with greater motor and apathy severity. Female sex and longer disease duration were associated with attenuated motor worsening. Antidepressant use was associated only with depression scores.
These longitudinal results support the differentiation of apathy and depression in PD. Like motor progression, apathy progression may be linked at least partially to dopaminergic neurodegeneration. Empirically-supported treatments for apathy in PD are needed.
Apathy; depression; antidepressants; structural equation modeling; neurodegeneration
Nanotechnology is the design and assembly of submicroscopic devices called nanoparticles, which are 1–100 nm in diameter. Nanomedicine is the application of nanotechnology for the diagnosis and treatment of human disease. Disease-specific receptors on the surface of cells provide useful targets for nanoparticles. Because nanoparticles can be engineered from components that (1) recognize disease at the cellular level, (2) are visible on imaging studies, and (3) deliver therapeutic compounds, nanotechnology is well suited for the diagnosis and treatment of a variety of diseases. Nanotechnology will enable earlier detection and treatment of diseases that are best treated in their initial stages, such as cancer. Advances in nanotechnology will also spur the discovery of new methods for delivery of therapeutic compounds, including genes and proteins, to diseased tissue. A myriad of nanostructured drugs with effective site-targeting can be developed by combining a diverse selection of targeting, diagnostic, and therapeutic components. Incorporating immune target specificity with nanostructures introduces a new type of treatment modality, nano-immunochemotherapy, for patients with cancer. In this review, we will discuss the development and potential applications of nanoscale platforms in medical diagnosis and treatment. To impact the care of patients with neurological diseases, advances in nanotechnology will require accelerated translation to the fields of brain mapping, CNS imaging, and nanoneurosurgery. Advances in nanoplatform, nano-imaging, and nano-drug delivery will drive the future development of nanomedicine, personalized medicine, and targeted therapy. We believe that the formation of a science, technology, medicine law–healthcare policy (STML) hub/center, which encourages collaboration among universities, medical centers, US government, industry, patient advocacy groups, charitable foundations, and philanthropists, could significantly facilitate such advancements and contribute to the translation of nanotechnology across medical disciplines.
Nanoplatforms; Nanotechnology; Image-guided therapy; Nanomedicine; Nanoneurosurgery; Nanostructures; Contrast agents; Nanoparticles; Nanotechnology policy; Nano-radiology; Nano-neuroscience; Nano-neurology
To test whether the synucleinopathies Parkinson’s disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson’s disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 × 1012; odds ratio 6.2).
Sinemet, a combination drug containing carbidopa and levodopa is considered the gold standard therapy for the treatment of Parkinson's disease (PD). When approved by the Food and Drug Administration (FDA) in 1988, a maximum daily dosage limit of 800 mg (eight tablets) of the 25/100 carbidopa/levodopa formulation was introduced. Overall, the FDA approval was a historic success; however, the pill limit has been hardcoded into many online medical record systems. This study investigates the 800 mg threshold by using a prospectively collected database of patient information.
A retrospective cohort study: (Part I) cross-sectional, (Part II) longitudinal.
Setting and participants
PD patients at a Movement Disorders Center in a large academic, tertiary medical setting.
An analysis was performed using carbidopa/levodopa at dosages below and above the 800 mg threshold. A secondary analysis was then performed using two consecutive clinic visits to determine the effects of crossing the 800 mg threshold. Comparisons were made on standardised scales.
There was no significant difference in motor, mood and quality-of-life scores in patients consuming below and above the 800 mg carbidopa/levodopa threshold, though a mild worsening in dyskinesia duration was noted without worsening in dyskinesia pain and disability. In PD patients who crossed the 800 mg threshold between two consecutive clinic visits, a significant improvement in depressive symptoms and quality-of-life measures was demonstrated, and in these patients there was no worsening of motor fluctuations or dyskinesia.
The data suggest that PD patients have the potential for enhanced clinical benefits when eclipsing the 800 mg carbidopa/levodopa threshold. Many patients will likely need to eclipse the 800 mg threshold and pharmacies and insurance companies should be aware of the requirements that may extend beyond approval limits.