Background Idiopathic Parkinson's disease (IPD) is characterized by the clinical motor symptoms of hypokinesia, rigidity, and tremor. Apart from these motor symptoms, cognitive deficits often occur in IPD. The positive effect of cholinesterase inhibitors on cognitive deficits in IPD and findings of earlier molecular imaging studies suggest that the cholinergic system plays an important role in the origin of cognitive decline in IPD. Methods Twenty-five non-demented patients with IPD underwent a 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380) SPECT to visualize α4β2 nicotinic acetylcholine receptors (nAchR) and cognitive testing with the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery to identify domains of cognitive dysfunction. Results In the CERAD, the IPD patients exhibited deficits in non-verbal memory, attention, psychomotor velocity, visuoconstructive ability, and executive functions. After Bonferroni correction for multiple comparisons, we found significant correlations between performance of the CERAD subtests Boston Naming Test (a specific test for visual perception and for detection of word-finding difficulties) and Word List Intrusions (a specific test for learning capacity and memory for language information) vs binding of α4β2 nAchR in cortical (the right superior parietal lobule) and subcortical areas (the left thalamus, the left posterior subcortical region, and the right posterior subcortical region). Conclusions These significant correlations between the results of the CERAD subtests and the cerebral α4β2 nAchR density, as assessed by 5-I-A-85380 SPECT, indicate that cerebral cholinergic pathways are relevant to cognitive processing in IPD.
BACKGROUND AND STUDY PURPOSE: High resolution imaging modalities and electroencephalographic studies (EEG) are used in the assessment of children with headaches. We evaluated the role of cerebral MRI (cMRI) and EEG in the initial assessment of children with headache as the chief complaint of initial presentation. METHODS: A retrospective chart analysis was performed at a tertiary University Hospital. RESULTS: 209 patients were included in this study [mean age 11.3 years; male 91 (43.5%); female 118 (56.5%)]. The following types of headaches were seen: Unclassified headache: 23.4%; probable migraine 17.2%, migraine without aura 13.4%, complicated migraine 12.4%, migraine with aura 1.0%; tension-type 15.3%, and cluster headaches 0.5%, and secondary headaches 16.7%. In 93 children (44.5%) abnormal physical/neurological findings were noted (multiple entries possible). On cMRI studies the following findings were seen: Infection of sinuses (7.2%), pineal cysts (2.4%), arachnoidial cyst and Chiari malformation (1.9%), unspecified signal enhancement (1.0%), and pituitary enlargement, inflammatory lesion, angioma, cerebral ischaemia, and intra-cerebral cyst (each 0.5%). Electroencephalographic findings included both focal and generalised abnormal slowing (5.3%) and Spike-wave complexes (3.3%). CONCLUSIONS: Despite abnormal findings on neurological/physical examination in a substantial number of children with headaches, the yield of pathological cMRIs was low. The use of EEG recordings was not contributory to the diagnostic and therapeutic approach. More research is needed to better define those patients who are likely to have an intracranial pathology.
Progranulin autoantibodies (PGRN) have been previously described in sera of patients with different autoimmune diseases such as ANCA associated vasculitis, large vessel vasculitis, Crohn9s disease, and psoriatic arthritis. Basically, progranulin seems to interact with TNF receptors 1 and 2 causing subsequently antiinflammatory effects. However, the presence of autoantibodies against progranulin was proved to result in lower serum progranulin levels, which is hypothesized to entertain proinflammatory environment due to lack of inhibited TNF alpha activity. Here we conducted a study evaluation the presence of PGRN in patients with rheumatoid arthritis, which is an autoimmune disorder with proven TNF alpha mediated joint inflammation.
Objectives
Prevalence of serum progranulin autoantibodies in RA with stratification into DAS28 subgroups with prognostic relevance.
Methods
From Nov 2011 till Dec 2013 sera of 307 RA patients (Saarland, Berlin) were collected and analyized for PGRN with ELISA (as previously published [1]) using a retrospective, blinded, non-randomized, two-center study design. All patients were on treatment with conventional DMARDs (n=193) or TNF inhibitors (n=114) at least for three months. All patients fullfill the ACR criteria from 1987 and the revised diagnostic EULAR/ACR criteria from 2011. RA patients characteristics concerning age, gender, treatment history, radiological joint imaging, and RF-/ACPA-serum status were availiable. DAS28 and HAQ representing RA activity were documented at study inclusion visit completed by the previous DAS28 scores as written in the patient9s chart under the same present antirheumatic treatment as availiable (retrospective analysis of data from three months till two years in the past).
Results
The overall prevalence of PGRN-Abs in RA patients was 26.6%. The RA patients were further stratifyied according to the lowest DAS 28 score during the observation period under the present treatment into patients with scores higher versus lower than 3.0 representing "good treatment response" or not, respectively. Table 1 demonstrates that the presence of PGRN-Abs is independent risk factor for failing "good treatment response" beyond erosive diesease, RF- and ACPA-positivity, HAQ score, and Larsen score in this setting.
Conclusions
PGRN-Abs in sera of RA patients seems to be predictive for poor response of conventional DMARDs and biological TNF-alpha blocking agents. However, further prospective studies with larger cohorts of RA patients are required to confirm the results.
