Free-water imaging in Parkinson's disease and atypical parkinsonism

Interesting and potentially important results here... imaging markers for PD and differentiation from atypical Parkinson's is essential... replication required but very promising results...

Brain. 2015 Dec 24. pii: awv361. [Epub ahead of print]

Planetta PJ, Ofori E, Pasternak O, Burciu RG, Shukla P, DeSimone JC, Okun MS, McFarland NR, Vaillancourt DE.

http://brain.oxfordjournals.org/content/early/2015/12/23/brain.awv361

Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease group comparisons, the support vector machine 10-fold cross-validation area under the curve was between 0.93-1.00 and there was high sensitivity and specificity. The regions and diffusion measures selected by the model varied across comparisons and are consistent with pathological studies. In conclusion, the current study used a novel bi-tensor diffusion analysis model to indicate that all forms of parkinsonism had elevated free-water in the substantia nigra. Beyond the substantia nigra, both multiple system atrophy and progressive supranuclear palsy, but not Parkinson's disease, showed a broad network of elevated free-water and altered free-water corrected fractional anisotropy that included the basal ganglia, thalamus, and cerebellum. These findings may be helpful in the differential diagnosis of parkinsonian disorders, and thereby facilitate the development and assessment of targeted therapies.

Parkinson disease male-to-female ratios increase with age: French nationwide study and meta-analysis.

This is an interesting result... and will be important not only for aetiological research into PD but also predictive modelling approaches...

J Neurol Neurosurg Psychiatry. 2015 Dec 23. pii: jnnp-2015-312283. doi: 10.1136/jnnp-2015-312283. [Epub ahead of print]

Moisan F, Kab S, Mohamed F, Canonico M, Le Guern M, Quintin C, Carcaillon L, Nicolau J, Duport N, Singh-Manoux A, Boussac-Zarebska M, Elbaz A.

http://jnnp.bmj.com/content/early/2015/12/23/jnnp-2015-312283.long

BACKGROUND:

Parkinson's disease (PD) is 1.5 times more frequent in men than women. Whether age modifies this ratio is unclear. We examined whether male-to-female (M-F) ratios change with age through a French nationwide prevalence/incidence study (2010) and a meta-analysis of incidence studies.

METHODS:

We used French national drug claims databases to identify PD cases using a validated algorithm. We computed M-F prevalence/incidence ratios overall and by age using Poisson regression. Ratios were regressed on age to estimate their annual change. We identified all PD incidence studies with age/sex-specific data, and performed a meta-analysis of M-F ratios.

RESULTS:

On the basis of 149 672 prevalent (50% women) and 25 438 incident (49% women) cases, age-standardised rates were higher in men (prevalence=2.865/1000; incidence=0.490/1000 person-years) than women (prevalence=1.934/1000; incidence=0.328/1000 person-years). The overall M-F ratio was 1.48 for prevalence and 1.49 for incidence. Prevalence and incidence M-F ratios increased by 0.05 and 0.14, respectively, per 10 years of age. Incidence was similar in men and women under 50 years (M-F ratio <1.2, p>0.20), and over 1.6 (p<0.001) times higher in men than women above 80 years (p trend <0.001). A meta-analysis of 22 incidence studies (14 126 cases, 46% women) confirmed that M-F ratios increased with age (0.26 per 10 years, p trend=0.005).

CONCLUSIONS:

Age-increasing M-F ratios suggest that PD aetiology changes with age. Sex-related risk/protective factors may play a different role across the continuum of age at onset. This finding may inform aetiological PD research.

Hepatitis C virus infection as a risk factor for Parkinson disease: A nationwide cohort study

Interesting observation... I don't remember seeing this before...

Neurology. 2015 Dec 23. pii: 10.1212/WNL.0000000000002307. [Epub ahead of print]

Tsai HH, Liou HH, Muo CH, Lee CZ, Yen RF, Kao CH.

OBJECTIVE:

To determine whether hepatitis C virus (HCV) infection is a risk factor for developing Parkinson disease (PD).

METHODS:

This nationwide population-based cohort study was based on data obtained from a dataset of the Taiwan National Health Insurance Research Database for the period 2000 to 2010. A total of 49,967 patients with viral hepatitis were included for analysis. Furthermore, 199,868 people without viral hepatitis were included for comparisons. Patients with viral hepatitis were further grouped into 3 cohorts: hepatitis B virus (HBV) infection, HCV infection, and HBV-HCV coinfection. In each cohort, we calculated the incidence of developing PD. A Cox proportional hazards model was applied to estimate the risk of developing PD in terms of hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS:

The crude HRs for developing PD was 0.66 (95% CI = 0.55-0.80) for HBV infection, 2.50 (95% CI = 2.07-3.02) for HCV infection, and 1.28 (95% CI = 0.88-1.85) for HBV-HCV coinfection. The association between HCV and PD remained statistically significant after adjustments for age, sex, and comorbidities (adjusted HR = 1.29, 95% CI = 1.06-1.56).

CONCLUSIONS:

We conducted a large nationwide population-based study and found that patients with HCV exhibit a significantly increased risk of developing PD.

Mendelian Randomization - the Key to Understanding Aspects of Parkinson's Disease Causation?

Nice early christmas present to have this published today... I anticipate this approach will take us forward in understanding the causal nature of Parkinson's... particularly when it comes to the associations with some of the stranger environmental exposures for PD...

Mov Disord. 2015 Dec 23. doi: 10.1002/mds.26492. [Epub ahead of print]

Noyce AJ, Nalls MA.

http://onlinelibrary.wiley.com/doi/10.1002/mds.26492/abstract

Parkinson's disease has multiple determinants and is associated with a wide range of exposures that appear to modify risk in traditional observational studies, including numerous lifestyle and environmental factors. Across other fields of medicine, Mendelian randomization has emerged as a powerful method to examine whether associations between exposures and disease outcomes are causal. Here we discuss the concept of Mendelian randomization, its potential relevance to Parkinson's disease, and suggest avenues through which the method could be employed to further understanding of the causal basis of Parkinson's disease.

Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker

Amazing how things change... 3-4 years ago there were a run of papers showing clear and definite differences in biopsies from GI tracts of patients in terms of staining for alpha-synuclein. Now there has been a run of studies showing no difference... I suspect the key lies in the final sentence of this abstract... the differences may be strain dependent... we should not give up on the gut...

Mov Disord. 2015 Dec 21. doi: 10.1002/mds.26473. [Epub ahead of print]

Chung SJ, Kim J, Lee HJ, Ryu HS, Kim K, Lee JH, Jung KW, Kim MJ, Kim MJ, Kim YJ, Yun SC, Lee JY, Hong SM, Myung SJ.

BACKGROUND:

Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals.

OBJECTIVES:

We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD.

METHODS:

We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity.

RESULTS:

No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P < 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD.

CONCLUSIONS:

The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains.

A scan without evidence is not evidence of absence: Scans without evidence of dopaminergic deficit in a symptomatic leucine-rich repeat kinase 2 mutation carrier.

Further evidence that radio-tracer imaging can be normal despite the presence of clear motor signs perhaps due to early compensatory mechanisms...

Mov Disord. 2015 Dec 21. doi: 10.1002/mds.26450. [Epub ahead of print]

Wile DJ, Dinelle K, Vafai N, McKenzie J, Tsui JK, Schaffer P, Ding YS, Farrer M, Sossi V, Stoessl AJ.

INTRODUCTION:

The basis for SWEDD is unclear, with most cases representing PD mimics but some later developing PD with a dopaminergic deficit.

METHODS:

We studied a patient initially diagnosed with SWEDD (based on 18 F-dopa PET) who developed unequivocal PD associated with a leucine-rich repeat kinase 2 p.G2019S mutation. Repeat multitracer PET was performed at 17 years' disease duration, including (+)[11C]dihydrotetrabenazine, [11C](N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine (which binds the serotonin transporter), and 18 F-dopa.

RESULTS:

The patient showed bilateral striatal dopaminergic denervation (right putamen 28% of age-matched normal, left putamen 33%). 18 F-dopa uptake was decreased, particularly on the left (mean 31% of normal vs. 45% on the more affected right side). Serotonin transporter binding was relatively preserved in the putamen (right mean 90% of normal, left 81%) and several cortical regions.

CONCLUSIONS:

SWEDD can occur in genetically determined PD and may, in some cases, be the result of compensatory nondopaminergic mechanisms operating in early disease.

Sporadic Parkinson's disease: development and distribution of α-synuclein pathology

An update on the neuropathology of sporadic PD...

Neuropathol Appl Neurobiol. 2015 Dec 13. doi: 10.1111/nan.12298. [Epub ahead of print]

Del Tredici K, Braak H.

http://onlinelibrary.wiley.com/doi/10.1111/nan.12298/abstract;jsessionid=F5CA9F77EACDD171E28C1580F36AE49F.f03t04

The development of α-synuclein-immunoreactive aggregates in selectively vulnerable neuronal types of the human central, peripheral, and enteric nervous systems is crucial for the pathogenesis of sporadic Parkinson's disease. The presence of these lesions persists into the end-phase of the disease, a process that is not subject to remission. The initial induction of α-synuclein misfolding and subsequent aggregation probably occurs in the olfactory bulb and/or the enteric nervous system. Each of these sites is exposed to potentially hostile environmental factors. Once formed, the aggregates appear to be capable of propagating transsynaptically from nerve cell to nerve cell in a virtually self-promoting pathological process. A regional distribution pattern of aggregated α-synuclein emerges that entails the involvement of only a few types of susceptible and axonally interconnected projection neurons within the human nervous system. One major route of disease progression may originate in the enteric nervous system and retrogradely reach the dorsal motor nucleus of the vagal nerve in the lower brainstem. From there, the disease process proceeds chiefly in a caudo-rostral direction through visceromotor and somatomotor brainstem centers to the midbrain, forebrain, and cerebral cortex. Spinal cord centers may become involved by means of descending projections from involved lower brainstem nuclei as well as by sympathetic projections connecting the enteric nervous system with postganglionic peripheral ganglia and preganglionic nuclei of the spinal cord. The development of experimental cellular and animal models is helping to explain the mechanisms of how abnormal α-synuclein can undergo aggregation and how transmission along axonal connectivities can occur, thereby encouraging the initiation of potential disease-modifying therapeutic strategies for sporadic Parkinson's disease.

Midlife milk consumption and substantia nigra neuron density at death

Clinico-pathological correlations between midlife milk consumption and observations made in the brains of subjects coming to post-mortem that did not have PD in life...

Neurology. 2015 Dec 9. pii: 10.1212/WNL.0000000000002254. [Epub ahead of print]

Abbott RD, Ross GW, Petrovitch H, Masaki KH, Launer LJ, Nelson JS, White LR, Tanner CM.

OBJECTIVE:

To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.

METHODS:

Milk intake data were collected from 1965 to 1968 in 449 men aged 45-68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm2) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.

RESULTS:

Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%-55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.

CONCLUSIONS:

Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.

"Gunslinger's gait": a new cause of unilaterally reduced arm swing.

This made me laugh earlier in the week... great article about the walking pattern of high-ranking Russian officials!

BMJ. 2015 Dec 14;351:h6141. doi: 10.1136/bmj.h6141.

Araújo R, Ferreira JJ, Antonini A, Bloem BR.

OBJECTIVE:

 To postulate a new possible cause of a unilaterally reduced arm swing in addition to the known medical conditions such as shoulder pathology, Erb's palsy, stroke, and Parkinson's disease.

METHODS:

 Analysis of YouTube videos depicting the gait of highly ranked Russian officials.

RESULTS:

 We found a similar walking pattern in President Vladimir Putin, Prime Minister Dmitry Medvedev and three other highly ranked Russian officials, all presenting with a consistently reduced right arm swing in the absence of other overt neurological abnormalities.

CONCLUSIONS:

 We propose that this new gait pattern, which we term "gunslinger's gait," may result from a behavioural adaptation, possibly triggered by KGB or other forms of weapons training where trainees are taught to keep their right hand close to the chest while walking, allowing them to quickly draw a gun when faced with a foe. This should be included in the differential diagnosis of a unilaterally reduced arm swing.

Whole-Exome Sequencing in Familial Parkinson Disease.

Here we see whole exome sequencing used to potentially uncover more of the missing heritability of PD...these now need to be confirmed in other data sets...

JAMA Neurol. 2015 Nov 23:1-8. doi: 10.1001/jamaneurol.2015.3266. [Epub ahead of print]

Farlow JL, Robak LA, Hetrick K, Bowling K, Boerwinkle E, Coban-Akdemir ZH, Gambin T, Gibbs RA, Gu S, Jain P, Jankovic J, Jhangiani S, Kaw K, Lai D, Lin H, Ling H, Liu Y, Lupski JR, Muzny D, Porter P, Pugh E, White J, Doheny K, Myers RM, Shulman JM, Foroud T.

http://archneur.jamanetwork.com/article.aspx?articleid=2470417

IMPORTANCE:

Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors.

OBJECTIVE:

To identify genetic variants contributing to disease risk in familial PD.

DESIGN, SETTING, AND PARTICIPANTS:

A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD.

MAIN OUTCOMES AND MEASURES:

Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design.

RESULTS:

The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing.

CONCLUSIONS AND RELEVANCE:

TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD.

Familial Aggregation and Co-Aggregation of Essential Tremor and Parkinson's Disease.

Certainly we see this in the clinic sometimes...

Neuroepidemiology. 2015 Nov 26;46(1):31-36. [Epub ahead of print]

Louis ED, Clark L, Ottman R.

http://www.karger.com/Article/Abstract/442021

BACKGROUND:

Current data suggest that the 2 common tremor disorders, essential tremor (ET) and Parkinson's disease (PD), may be associated with one another. Familial aggregation studies allow one to further explore their relatedness.

METHODS:

Probands with ET (n = 110), PD (n = 130) or both ET and PD (n = 27) and control probands (n = 177) reported whether they had relatives with these diseases or with non-specific tremor.

RESULTS:

A greater proportion of ET probands than control probands reported relatives with ET (30.0 vs. 2.8%, p < 0.001), non-specific tremor (38.2 vs. 13.6%, p < 0.001) and both ET and PD in different relatives (6.4 vs. 0.6%, p = 0.004). A greater proportion of PD probands than control probands reported relatives with PD (20.0 vs. 8.5%, p = 0.003), ET (11.5 vs. 2.8%, p = 0.002) and both ET and PD in different relatives (6.9 vs. 0.6%, p = 0.002).

CONCLUSIONS:

This study provides evidence for the aggregation of ET in ET families and PD in PD families, and the familial co-aggregation of ET and PD.

Oculo-Visual Dysfunction in Parkinson's Disease.

Oculo-visual disturbance is frequently reported in PD. Further characterisation and recognition of when it begins are important, but difficult to study formally. Efforts close to home are underway...!

J Parkinsons Dis. 2015 Nov 24. [Epub ahead of print]

Armstrong RA

http://content.iospress.com/articles/journal-of-parkinsons-disease/jpd150686

This review describes the oculo-visual problems likely to be encountered in Parkinson's disease (PD) with special reference to three questions: (1) are there visual symptoms characteristic of the prodromal phase of PD, (2) is PD dementia associated with specific visual changes, and (3) can visual symptoms help in the differential diagnosis of the parkinsonian syndromes, viz. PD, progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and corticobasal degeneration (CBD)? Oculo-visual dysfunction in PD can involve visual acuity, dynamic contrast sensitivity, colour discrimination, pupil reactivity, eye movement, motion perception, and visual processing speeds. In addition, disturbance of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations may be present. Prodromal features of PD may include autonomic system dysfunction potentially affecting pupil reactivity, abnormal colour vision, abnormal stereopsis associated with postural instability, defects in smooth pursuit eye movements, and deficits in visuo-motor adaptation, especially when accompanied by idiopathic rapid eye movement (REM) sleep behaviour disorder. PD dementia is associated with the exacerbation of many oculo-visual problems but those involving eye movements, visuo-spatial function, and visual hallucinations are most characteristic. Useful diagnostic features in differentiating the parkinsonian symptoms are the presence of visual hallucinations, visuo-spatial problems, and variation in saccadic eye movement dysfunction.

Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression

We are starting to learn much more about the genetic architecture of PD and how genes determine not only ones absolute risk of acquiring PD, but also account for a substantial proportion of the heterogeneity of PD.

Neurobiol Aging. 2015 Sep 30. pii: S0197-4580(15)00471-6. doi: 10.1016/j.neurobiolaging.2015.09.014. [Epub ahead of print]

Davis AA, Andruska KM, Benitez BA, Racette BA, Perlmutter JS, Cruchaga C.

http://www.neurobiologyofaging.org/article/S0197-4580(15)00471-6/abstract

Multiple genetic variants have been linked to risk of Parkinson disease (PD), but known mutations do not explain a large proportion of the total PD cases. Similarly, multiple loci have been associated with PD risk by genome-wide association studies (GWAS). The influence that genetic factors confer on phenotypic diversity remains unclear. Few studies have been performed to determine whether the GWAS loci are also associated with age at onset (AAO) or motor progression. We used 2 PD case-control data sets (Washington University and the Parkinson's Progression Markers Initiative) to determine whether polymorphisms located at the GWAS top hits (GBA, ACMSD/TMEM163, STK39, MCCC1/LAMP3, GAK/TMEM175, SNCA, and MAPT) show association with AAO or motor progression. We found associations between single nucleotide polymorphisms at the GBA and MAPT loci and PD AAO and progression. These findings reinforce the complex genetic basis of PD and suggest that distinct genes and variants explain the genetic architecture of PD risk, onset, and progression.

Skin nerve misfolded α-synuclein in pure autonomic failure and Parkinson disease.

Very interesting to see the continuation of the work of this group following the first report in 2014...especially given the strong results presented. Phosphorylated alpha-syn in biopsies from all subjects with a syncucleinopathy (PD and PAF) and the importance of the site of sampling reiterated.

Ann Neurol. 2015 Nov 25. doi: 10.1002/ana.24567. [Epub ahead of print]

Donadio V, Incensi A, Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, Liguori R.

http://onlinelibrary.wiley.com/doi/10.1002/ana.24567/abstract;jsessionid=7A6E9ECDDD66E229E7E0375AC6674498.f02t01?systemMessage=Wiley+Online+Library+will+have+be+unavailable+on+Saturday+5th+December+from+10%3A00-14%3A00+GMT+%2F+05%3A00-09%3A00+EST+%2F+18%3A00-22%3A00+SGT+for+essential+maintenance.+Apologies+for+the+inconvenience.

OBJECTIVE:

To characterize the expression in skin nerves of native (n-syn) and misfolded phosphorylated (p-syn) α-synucleins in pure autonomic failure (PAF) and idiopathic Parkinson disease (IPD). The specific aims were to: 1) define the importance of n-syn and p-syn as disease biomarkers; 2) ascertain differences in abnormal synuclein skin nerve deposits.

MATERIALS AND METHODS:

We studied 30 patients including 16 well-characterized IPD and 14 patients fulfilling PAF diagnostic criteria and 15 age-matched controls. Subjects underwent skin biopsy from proximal (i.e. cervical) and distal (i.e. thigh and leg) sites to study small nerve fiber and intraneural n-syn and p-syn.

RESULTS:

PAF and IPD showed a length-dependent somatic and autonomic small fiber loss, more severely expressed in patients with higher p-syn load. N-syn was similarly expressed in both groups of patients and controls. By contrast, p-syn was not evident in any skin sample of controls but was found in all PAF and IPD patients whilst with different skin innervation. In addition, abnormal α-syn deposits were found in all analyzed skin samples in PAF but in only 49% of samples with a higher positivity rate in the proximal site in IPD.

INTERPRETATION:

1) Intraneural p-syn was a reliable in vivo marker of PAF and IPD; 2) neuritic p-syn inclusions differed in PAF and IPD suggesting a different underlying pathogenesis; 3) searching for abnormal p-syn deposits in skin nerves, the site of analysis is irrelevant in PAF but it is critical in IPD.

Evaluation of 99mTc-TRODAT-1 SPECT in the diagnosis of Parkinson's disease versus other progressive movement disorders

Consistent with previous studies, there is little to differentiate Parkinson's disease from parkinsonian syndromes here, but as expected essential tremor and vascular PD subjects have better uptake...

Ann Nucl Med. 2015 Nov 26. [Epub ahead of print]

Fallahi B, Esmaeili A, Beiki D, Oveisgharan S, Noorollahi-Moghaddam H, Erfani M, Tafakhori A, Rohani M, Fard-Esfahani A, Emami-Ardekani A, Geramifar P, Eftekhari M.

http://link.springer.com/article/10.1007%2Fs12149-015-1042-y

OBJECTIVE:

Parkinson disease (PD), parkinsonian syndromes (PS) and essential tremor (ET) are different types of movement disorders which share some symptoms resulting in a difficulty of certain diagnosis. This study was conducted to determine the value of 99mTc-TRODAT-1 scan to differentiate PD from ET and other PS cases.

METHODS:

Totally, 75 patients were studied including 29 PD, 6 possible PD, 22 ET and 18 PS cases. A dual-head SPECT-CT was used to perform basal ganglia (BG) imaging following administration of 99mTc-TRODAT-1. The BG uptake values were normalized to whole brain and occipital activity. All patients were followed for 2-22 months to reach a certain diagnosis.

RESULTS:

Patients with ET and drug-induced parkinsonism show significantly higher normalized BG uptake as compared to the other subgroups; however, no significant difference was noted between PD and PS patients. The sensitivity and specificity of the findings for the differentiation between patients with the disease associated versus not associated with BG dysfunction were 80 and 83.3 %, respectively. A predictive positive value of 82.6 % was obtained using an additive scaling index defined as asymmetry and unevenness of uptake in putamen and/or caudate contralateral to the dominant side of current symptoms.

CONCLUSIONS:

99mTc-TRODAT-1 scan is an appropriate method to differentiate PD or PS versus ET. A combination of scan pattern including asymmetry of BG uptake and unevenness of activity in caudate and putamen along with the side of dominant symptoms may be valuable for the differentiation of Parkinson's disease from the other parkinsonian syndromes.