The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients

The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy

Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy

Spine Topographical Distribution of Skin \u3b1-Synuclein Deposits in Idiopathic Parkinson Disease

Phosphorylated \u3b1-synuclein (p-syn) in skin nerves mainly in the proximal sites is a promising neurodegenerative biomarker for idiopathic Parkinson disease (IPD). However, the p-syn spine distribution particularly in patients with unilateral motor dysfunctions remains undefined. This study aimed to investigate in IPD p-syn differences between left and right cervical spine sites in patients with prevalent unilateral motor symptoms, and cervical and thoracic spine sites in patients with bilateral motor symptoms. We enrolled 28 IPD patients fulfilling clinical diagnostic criteria associated with abnormal nigro-striatal DatScan and cardiac MIBG: 15 with prevalently unilateral motor symptoms demonstrated by DatScan; 13 with bilateral motor symptoms and DatScan abnormalities. Patients underwent skin biopsy searching for intraneural p-syn deposits: skin samples were taken from C7 paravertebral left and right sites in unilateral patients and from cervical (C7) and thoracic (Th12) paravertebral spine regions in bilateral patients. Unilateral patients displayed 20% of abnormal p-syn deposits in the affected motor site, 60% in both sites and 20% only in the non-affected site. P-syn was found in all patients in C7 but in only 62% of patients in Th12. Our data showed that cervical p-syn deposits displayed a uniform distribution between both sides not following the motor dysfunction in unilateral patients, and skin nerve p-syn deposits demonstrated a spine gradient with the cervical site expressing the highest positivity

Effects on cognition of 20-day anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex in patients affected by mild cognitive impairment: a case-control study

Mild cognitive impairment (MCI) is a common disorder affecting as much as 15% of the elderly population. Transcranial direct current stimulation (tDCS) is a non-invasive technique of neuromodulation that has proven to influence performance in different cognitive domains

In Vivo Diagnosis of Synucleinopathies: A Comparative Study of Skin Biopsy and RT-QuIC

none13siTo determine whether: 1) the immunofluorescence (IF) is a reproducible technique in detecting misfolded α-synuclein (α-syn) in skin nerves; and subsequently 2) IF and RT-QuIC (both in skin and CSF) show a comparable in vivo diagnostic accuracy in distinguish synucleinopathies (SOPs) from non-synucleinopathies (non-SOPs) in a large cohort of patients.noneDonadio, Vincenzo; Wang, Zerui; Incensi, Alex; Rizzo, Giovanni; Fileccia, Enrico; Vacchiano, Veria; Capellari, Sabina; Magnani, Martina; Scaglione, Cesa; Stanzani Maserati, Michelangelo; Avoni, Patrizia; Liguori, Rocco; Zou, WenquanDonadio, Vincenzo; Wang, Zerui; Incensi, Alex; Rizzo, Giovanni; Fileccia, Enrico; Vacchiano, Veria; Capellari, Sabina; Magnani, Martina; Scaglione, Cesa; Stanzani Maserati, Michelangelo; Avoni, Patrizia; Liguori, Rocco; Zou, Wenqua

Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis

Neurofilament light chain protein (NfL) is currently the most accurate cerebrospinal fluid (CSF) biomarker in amyotrophic lateral sclerosis (ALS) in terms of both diagnostic and prognostic value, but the mechanism underlying its increase is still a matter of debate. Similarly, emerging CSF biomarkers of neurodegeneration and neuroinflammation showed promising results, although further studies are needed to clarify their clinical and pathophysiological roles. In the present study we compared the diagnostic accuracy of CSF NfL, phosphorylated (p)-tau/total (t)-tau ratio, chitinase-3-like protein 1 (YKL-40) and chitotriosidase 1 (CHIT1), in healthy controls (n\u2009=\u200943) and subjects with ALS (n\u2009=\u200980) or ALS mimics (n\u2009=\u200946). In ALS cases, we also investigated the association between biomarker levels and clinical variables, the extent of upper motor neuron (UMN) and lower motor neuron (LMN) degeneration, and denervation activity through electromyography (EMG). ALS patients showed higher levels of CSF NfL, YKL-40, CHIT1, and lower values of p-tau/t-tau ratio compared to both controls and ALS mimics. Among all biomarkers, NfL yielded the highest diagnostic performance (>\u200990% sensitivity and specificity) and was the best predictor of disease progression rate and survival in ALS. NfL levels showed a significant  correlation with the extent of LMN involvement, whereas YKL-40 levels increased together with the number of areas showing both UMN and LMN damage. EMG denervation activity did not correlate with any CSF biomarker change. These findings confirm the highest value of NfL among currently available CSF biomarkers for the diagnostic and prognostic assessment of ALS and contribute to the understanding of the pathophysiological and electrophysiological correlates of biomarker changes

Clinical and laboratory findings in patients with Fabry disease.

<p>Clinical and laboratory findings in patients with Fabry disease.</p

Skin Gb3 deposits in FD patients with classical GLA mutation.

<p>Confocal microscope (x40 in A and B; x60 in C) study of Gb3 in skin vessels (A, AI and AII), sweat gland tubules (B, BI and BII) and arrector pilorum muscle (C, CI and CII). A) Skin arterioles showed no Gb3 deposits in the control subject (A). However, these abnormal deposits were abundant in the male FD patient in the wall of the arteriole and its endothelium (AII) and less evident in the female patient (AI); B) Sweat gland tubules of the control showed no Gb3 deposits (B), which were found in the male with FD (BII). The female showed nearly absent Gb3 deposits inside the sweat gland tubules (BI); C) Arrector pilorum muscle cells of the control have no Gb3 deposits (C) but they were found in the male (CII) and less in female FD patient (CI).</p

Comparison between patients with classical (skin Gb3 positive) and non-classical (Gb3 negative) GLA mutations.

<p>Comparison between patients with classical (skin Gb3 positive) and non-classical (Gb3 negative) GLA mutations.</p