Clinical profile of parkinsonism and Parkinson's disease in Lagos, Southwestern Nigeria

<p>Abstract</p> <p>Background</p> <p>Current data on the pattern of parkinsonism and Parkinson's disease in Nigerians are sparse.</p> <p>This database was designed to document the clinical profile of PD in Nigerians, and compare this to prior observations.</p> <p>Methods</p> <p>A database of patients presenting to the Neurology out-patients clinic of the Lagos University Teaching Hospital was established in October 1996. Demographic and clinical data at presentation (disease stage using Hoehn and Yahr scale; 'off' state severity on the Unified Parkinson's disease Rating Scale) were documented for patients diagnosed with parkinsonism between October 1996 and December 2006. Cases were classified as Parkinson's disease or secondary parkinsonism (in the presence of criteria suggestive of a secondary aetiology).</p> <p>Results</p> <p>The hospital frequency of parkinsonism (over a 2-year period, and relative to other neurologic disorders) was 1.47% (i.e. 20/1360). Of the 124 patients with parkinsonism, 98 (79.0%) had PD, while 26 (21.0%) had secondary parkinsonism. Mean age (SD) at onset of PD (61.5 (10.0) years) was slightly higher than for secondary parkinsonism (57.5 (14.0) years) (P = 0.10). There was a male preponderance in PD (3.3 to 1) and secondary parkinsonism (2.7 to 1), while a positive family history of parkinsonism was present in only 1.02% (1/98) of PD. There was a modestly significant difference in age at onset (SD) of PD in men (60.3 (10.4)) compared to women (65.2 (7.9)) (T = 2.08; P = 0.04). The frequency of young onset PD (≤ 50 years) was 16.3% (16/98). The mean time interval from onset of motor symptoms to diagnosis of PD was 24.6 ± 26.1 months with majority presenting at a median 12 months from onset. On the H&Y scale, severity of PD at presentation was a median 2.0 (range 1 to 4). PD disease subtype was tremor-dominant in 31 (31.6%), mixed 54 (55.1%) and akinetic-rigid 14 (14.3%). Hypertension was present as a co-morbidity in 20 (20.4%), and diabetes in 6 (6.12%).</p> <p>Conclusions</p> <p>The clinical profile of PD in Nigerians is similar to that in other populations, but is characterized by delayed presentation as has been reported in other developing countries. Young-onset disease occurs but may be less commonly encountered, and frequency of a positive family history is lower than in western populations.</p

A New Evolutionary Algorithm-Based Home Monitoring Device for Parkinson’s Dyskinesia

Parkinson’s disease (PD) is a neurodegenerative movement disorder. Although there is no cure, symptomatic treatments are available and can significantly improve quality of life. The motor, or movement, features of PD are caused by reduced production of the neurotransmitter dopamine. Dopamine deficiency is most often treated using dopamine replacement therapy. However, this therapy can itself lead to further motor abnormalities referred to as dyskinesia. Dyskinesia consists of involuntary jerking movements and muscle spasms, which can often be violent. To minimise dyskinesia, it is necessary to accurately titrate the amount of medication given and monitor a patient’s movements. In this paper, we describe a new home monitoring device that allows dyskinesia to be measured as a patient goes about their daily activities, providing information that can assist clinicians when making changes to medication regimens. The device uses a predictive model of dyskinesia that was trained by an evolutionary algorithm, and achieves AUC>0.9 when discriminating clinically significant dyskinesia

Amyotrophic lateral sclerosis-motor neuron disease, monoclonal gammopathy, hyperparathyroidism, and B12 deficiency: case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Amyotrophic lateral sclerosis (the most common form of motor neuron disease) is a progressive and devastating disease involving both lower and upper motor neurons, typically following a relentless path towards death. Given the gravity of this diagnosis, all efforts must be made by the clinician to exclude alternative and more treatable entities. Frequent serology testing involves searching for treatable disorders, including vitamin B12 deficiency, parathyroid anomalies, and monoclonal gammopathies.</p> <p>Case presentation</p> <p>We present the case of a 78-year-old Caucasian man with all three of the aforementioned commonly searched for disorders during an investigation for amyotrophic lateral sclerosis.</p> <p>Conclusions</p> <p>The clinical utility of these common tests and what they ultimately mean in patients with amyotrophic lateral sclerosis is discussed, along with a review of the literature.</p

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease

beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual case

Loss of Nuclear Activity of the FBXO7 Protein in Patients with Parkinsonian-Pyramidal Syndrome (PARK15)

Mutations in the F-box only protein 7 gene (FBXO7) cause PARK15, an autosomal recessive neurodegenerative disease presenting with severe levodopa-responsive parkinsonism and pyramidal disturbances. Understanding the PARK15 pathogenesis might thus provide clues on the mechanisms of maintenance of brain dopaminergic neurons, the same which are lost in Parkinson's disease. The protein(s) encoded by FBXO7 remain very poorly characterized. Here, we show that two protein isoforms are expressed from the FBXO7 gene in normal human cells. The isoform 1 is more abundant, particularly in primary skin fibroblasts. Both isoforms are undetectable in cell lines from the PARK15 patient of an Italian family; the isoform 1 is undetectable and the isoform 2 is severely decreased in the patients from a Dutch PARK15 family. In human cell lines and mouse primary neurons, the endogenous or over-expressed, wild type FBXO7 isoform 1 displays mostly a diffuse nuclear localization. An intact N-terminus is needed for the nuclear FBXO7 localization, as N-terminal modification by PARK15-linked missense mutation, or N-terminus tag leads to cytoplasmic mislocalization. Furthermore, the N-terminus of wild type FBXO7 (but not of mutant FBXO7) is able to confer nuclear localization to profilin (a cytoplasmic protein). Our data also suggest that overexpressed mutant FBXO7 proteins (T22M, R378G and R498X) have decreased stability compared to their wild type counterpart. In human brain, FBXO7 immunoreactivity was highest in the nuclei of neurons throughout the cerebral cortex, intermediate in the globus pallidum and the substantia nigra, and lowest in the hippocampus and cerebellum. In conclusion, the common cellular abnormality found in the PARK15 patients from the Dutch and Italian families is the depletion of the FBXO7 isoform 1, which normally localizes in the cell nucleus. The activity of FBXO7 in the nucleus appears therefore crucial for the maintenance of brain neurons and the pathogenesis of PARK15

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise

Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645–1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second author’s name was presented incorrectly. The author’s name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Dual Beneficial Effects of (-)-Epigallocatechin-3-Gallate on Levodopa Methylation and Hippocampal Neurodegeneration: In Vitro and In Vivo Studies

A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models.METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology.RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies.CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications. British Journal of Cancer (2009) 101, 645-657. doi: 10.1038/sj.bjc.6605200 www.bjcancer.com Published online 21 July 2009 (C) 2009 Cancer Research U

Herbal Medicines for Parkinson's Disease: A Systematic Review of Randomized Controlled Trials

OBJECTIVE: We conducted systematic review to evaluate current evidence of herbal medicines (HMs) for Parkinson's disease (PD). METHODS: Along with hand searches, relevant literatures were located from the electronic databases including CENTRAL, MEDLINE, EMBASE, CINAHL, AMED, PsycInfo, CNKI, 7 Korean Medical Databases and J-East until August, 2010 without language and publication status. Randomized controlled trials (RCTs), quasi-randomized controlled trials and randomized crossover trials, which evaluate HMs for idiopathic PD were selected for this review. Two independent authors extracted data from the relevant literatures and any disagreement was solved by discussion. RESULTS: From the 3432 of relevant literatures, 64 were included. We failed to suggest overall estimates of treatment effects on PD because of the wide heterogeneity of used herbal recipes and study designs in the included studies. When compared with placebo, specific effects were not observed in favor of HMs definitely. Direct comparison with conventional drugs suggested that there was no evidence of better effect for HMs. Many studies compared combination therapy with single active drugs and combination therapy showed significant improvement in PD related outcomes and decrease in the dose of anti-Parkinson's drugs with low adverse events rate. CONCLUSION: Currently, there is no conclusive evidence about the effectiveness and efficacy of HMs on PD. For establishing clinical evidence of HMs on PD, rigorous RCTs with sufficient statistical power should be promoted in future