[Effects of electroacupuncture on ethology, microglia activation and P2X7 receptor expression in periaqueductal gray in rats with migraine].

OBJECTIVE: To observe the effects of electroacupuncture(EA) at "Fengchi"(GB20) on the ethology, microglia activation and P2X7 receptor(P2X7R) expression in the periaqueductal gray(PAG) in recurrent migraine rat model, so as to explore the underlying mechanism of EA reducing central sensitization of migraine. METHODS: Thirty-six male SD rats were randomly divided into control, model and EA groups, with 12 rats in each group. Recurrent migraine model was induced using repea-ted dural electrical stimulation once another day(the 1st, 3rd, 5th, 7th and 9th days), for a total of 5 times; rats in the EA group received EA treatment(2 Hz/15 Hz, 0.8-1 mA) at GB20 after dural electrical stimulation, for 10 min every time, once a day for 9 days; rats in the control group only received electrode placement. The facial and hindpaw mechanical withdrawal threshold was detected by using an electronic von-Frey on the 0th(baseline), 2nd, 4th, 6th, and 8th days. Microglia activation in the PAG was evaluated by using immunofluorescence staining to detect the number of ionized calcium binding adaptor molecule-1(Iba-1)-labeled microglia. Expression levels of microglia marker Iba-1, inflammatory factor interleukin(IL)-1ß and P2X7R were detected by Western blot. RESULTS: Compared with the control group, the facial and hindpaw mechanical withdrawal threshold of rats were significantly reduced on the 2nd, 4th, 6th, and 8th days(P<0.01，P<0.001); the microglia in the PAG area were significantly activated, with the number of Iba-1-positive microglia, and the expression levels of Iba-1, IL-1ß and P2X7R proteins significant increased(P<0.001, P<0.05) in the model group. Compared with the model group, the facial and hindpaw mechanical withdrawal threshold of rats were significantly increased on the 4th, 6th, and 8th days(P<0.05，P<0.001，P<0.01), and the above indicators were significantly reversed (P<0.05) in the EA group. CONCLUSION: EA at GB20 can significantly improve facial and hindpaw mechanical withdrawal threshold of migraine rats, and its possible mechanism may be related to inhibiting microglia activation mediated by P2X7R in the PAG.

Adult-onset Krabbe disease presenting with progressive myoclonic epilepsy and asymmetric occipital lesions: A case report.

Krabbe disease (KD), also known as globoid cell leukodystrophy, is a rare autosomal recessive condition caused by mutations in the galactocerebrosidase (GALC) gene. KD is more common in infants and young children than in adults. We reported the case of an adult-onset KD presenting with progressive myoclonic epilepsy (PME) and cortical lesions mimicking mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. The whole-exome sequencing (WES) identified a pathogenic homozygous missense mutation of the GALC gene. Parents of the patient were heterozygous for the mutation. The clinical, electrophysiological, and radiological data of the patient were retrospectively analyzed. The patient was a 24-year-old woman presenting with generalized seizures, progressive cognitive decline, psychiatric symptoms, gait ataxia, and action-induced myoclonus. The brain magnetic resonance imaging (MRI) revealed a right occipital cortical ribbon sign without any other damage. This single case expands the clinical phenotypes of adult-onset KD.

Musculoskeletal Pain in Parkinson's Disease.

BACKGROUND: Musculoskeletal pain is commonly experienced in patients with Parkinson's disease (PD). Few studies have investigated the clinical characteristics and risk factors associated with musculoskeletal pain. OBJECTIVES: To investigate the distribution, clinical characteristics, and factors associated with musculoskeletal pain in a large sample of patients with PD. METHODS: We enrolled 452 patients from two clinics and used a standardized questionnaire to collect demographic and clinical information. Musculoskeletal pain was diagnosed based on the Ford Classification System, and pain severity was assessed with the numeric rating scale (NRS). Multivariate regression models explored the association between clinical features of PD and quality of life and pain. RESULTS: Two hundred and six patients (45.58%) reported musculoskeletal pain, typically in their lower limbs and backs. Levodopa resulted in a ≥30% reduction in pain intensity scores in 170 subjects. Female sex (odds ratio [OR], 1.57; 95% CI, 1.07-2.29) and Levodopa-equivalent daily doses (LEDDs; OR, 3.35; 95% CI, 1.63-6.59) were associated with an increased risk for musculoskeletal pain. Pain duration (p = 0.017), motor symptoms (p < 0.001), and depression (p < 0.001) were significantly associated with quality of life. CONCLUSIONS: The lower limbs and back are common sites of musculoskeletal pain in patients with PD, and up to 82.52% of patients were responsive to Levodopa. Female sex and LEDDs are associated with musculoskeletal pain, suggesting that dopamine deficiencies, and not the motor and non-motor impairment, might be the most critical baseline risk factor of musculoskeletal pain.

Gandouling Tablets Inhibit Excessive Mitophagy in Toxic Milk (TX) Model Mouse of Wilson Disease via Pink1/Parkin Pathway.

OBJECTIVE: Gandouling (GDL) tablet is a Chinese patent medicine approved by the National Medical Product Administration, which is used to treat Wilson disease (WD) in China. In this study, we aimed to investigate the effects of GDL on mitophagy in the hippocampus in the toxic milk (TX) mouse model of WD. METHODS: Mice were randomly divided into the following four groups: control, Wilson (model group), D-penicillamine (DPA), and GDL groups. The animal behaviors were evaluated by the water maze experiment, traction test, and pole test. Transmission electron microscopy was used for the detection of mitochondrion structure. An enzyme-linked immunosorbent assay (ELISA) was performed for the analysis of the changes in liver function. Colocalization of mitophagy-related proteins was detected by fluorescence microscopy. Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were conducted for the detection of protein expression and mRNA levels, respectively. RESULTS: Significant reduction in neurological impairments was observed in the WD model group. All of these results were significantly reversed by GDL intervention. Compared with the levels in the Wilson group, the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), and albumin (ALB) changed obviously. Colocalization between mitophagy-related proteins pink1, parkin, and mitochondria was changed significantly. The mitophagy-related mRNA (pink1, parkin, and LC3II) and protein expression levels (pink1, parkin, and the rate of LC3II/LC3I) were decreased significantly, while p62 was remarkably increased after GDL intervention. CONCLUSION: Our findings indicated that the neuroprotective mechanism of GDL may occur via the inhibition of excessive mitophagy through the regulation of the pink1/parkin pathway in the TX mouse brain of WD.

Acute onset neurological symptoms in Wilson disease after traumatic, surgical or emotional events: A cross-sectional study.

Acute onset neurological symptoms evoked by traumatic, surgical, or emotional events in Wilson disease (WD) have never been reported and its clinical characteristics are unclear.We aimed to summarize the clinical characteristics of a special WD whose neurological symptoms acutely developed after traumatic, surgical, or emotional events.Retrospective pilot study.Thirty-one patients who had acute onset neurological symptom as an initial presentation of WD or a new presentation of hepatic WD after mild trauma, surgery, or emotional events were retrospectively studied. All patients were followed for half to 1 year after regular anti-copper treatment.The averaged latency for neurological symptom presentation was 2.79 ±â€Š1.21 hours. The most frequent neurological symptoms were tremor (74%) and basal ganglia (BG) lesions were detected on magnetic resonance imaging in all patients. Lesions in other regions were much less frequently detected. Neurological symptom score and its recovery after treatment were correlated with lesion location: BG area and BG plus other brain areas. Neurological symptoms improved in 21 patients who received timely anti-copper treatment but continued to deteriorate in 6 patients who did not accept regular anti-copper treatment for delayed diagnosis.A diagnosis of WD should be considered when adolescents or adults experience acute presentation of extrapyramidal systems after traumatic, surgical, or emotional stimulation. Timely anti-copper therapy usually gives rise to an excellent prognosis.

Successful Treatment of Hypersplenism in Wilson's Disease by Partial Splenic Embolization.

AIM: Hypersplenism can occur in patients with Wilson's disease (WD). Surgical splenectomy is a conventional treatment for this condition; however, emotional and neurological deterioration may follow splenectomy. In recent years, partial splenic embolization (PSE) has been increasingly performed as a nonsurgical alternative treatment for hypersplenism. The aim of this study was to evaluate the effectiveness and safety of PSE compared with splenectomy in the treatment of hypersplenism in WD patients. METHODS: Fifty WD patients with hypersplenism were randomly divided into two groups (group A and group B), each including 25 patients. Patients in groups A and B were treated with PSE and splenectomy, respectively. Data were collected on the clinical efficacy of each procedure, adverse reactions, hematologic and blood chemistry test results, and abdominal computed tomography (CT) scan findings (group A only). RESULTS: Marked improvements in the platelet and leukocyte counts after PSE and splenectomy were observed in all patients. PSE was associated with improved liver function without severe complications, and no significant changes in emotional and neurological symptoms were observed. In contrast, seven WD patients suffered neurological deterioration after splenectomy. CONCLUSIONS: Hypersplenism in WD patients was successfully treated by PSE, which appears to be a safe and effective alternative treatment for WD-induced hypersplenism.

[Effect of Electroacupuncture on Expression of 5-HT7 Receptor in Periaqueductal Gray and Plasma Calcitonin Gene-related Peptide in Migraine Rats].

OBJECTIVE: To explore the analgesic effect of electroacupuncture(EA)by modulating 5-hydroxytryptamine 7 (5-HT7) receptor in periaqueductal gray (PAG) and plasma calcitonin gene-related peptide (CGRP). METHODS: Forty-two male Sprague Dawley (SD) rats were randomly divided into control，model and EA groups, 14 rat in each one. The neurogenic migraine model was established by repeated electrical stimulation on sagittal sinus duramater. Intracranial electrodes were used in the control group without stimuli. The rats in the EA group received EA (0.5－1 mA, 2 Hz/15 Hz) at "Fengchi" (GB 20) for 10 min after dural electrical stimulation, once a day for 6 days. The expression of 5-HT7 receptor in the PAG was assessed by immunofluorescence and Western blot, respectively; plasma CGRP was measured by radioimmunoassay. RESULTS: Compared with the control group, the positive neuron number and protein expression of 5-HT7 receptor in PAG and plasma CGRP increased after model establishment (all P<0.001). The above mentioned indexes were reversed in the EA group compared with those in the model group (the positive neuron number and protein expression of 5-HT7 receptor, P<0.01; plasma CGRP, P<0.05). CONCLUSIONS: EA at GB 20 can down-regulate the expression of 5-HT7 receptor in the PAG and reduce the content of plasma CGRP in the rats of migraine.

Successful Splenectomy for Hypersplenism in Wilson's Disease: A Single Center Experience from China.

Splenomegaly and pancytopenia are common in Wilson's disease (WD) and splenectomy is one of the conventional treatments for splenomegaly and the associated pancytopenia. However, splenectomy remained controversial for hypersplenism in WD as it was reported that splenectomy leaded to serious emotional and neurological deterioration in WD patients with hypersplenism. In the current study, we present our experiences in 70 WD patients with hypersplenism who had undergone splenectomy, outlining the safety and efficacy of splenectomy in WD. The clinical database of 70 WD patients with hypersplenism who had undergone splenectomy in our hospital between 2009 and 2013 were reviewed and followed-up regularly. Before splenectomy, all the patients accepted a short period of anti-copper treatment with intravenous sodium 2, 3-dimercapto-1-propane sulfonate (DMPS). All the patients demonstrated a marked improvement in platelet and leucocyte counts after splenectomy. No severe postoperative complication was observed. In particular, none of the 37 patients with mixed neurologic and hepatic presentations experienced neurological deterioration after splenectomy, and none of the patients with only hepatic presentations newly developed neurological symptoms. During the one year follow-up period, no patient presented hepatic failure or hepatic encephalopathy, no hepatic patient newly developed neurological presentations, and only 3 patients with mixed neurologic and hepatic presentations suffered neurological deterioration and these 3 patients had poor compliance of anti-copper treatment. Quantative analysis of the neurological symptoms in the 37 patients using the Unified Wilson's Disease Rating Scale (UWDRS) showed that the neurological symptoms were not changed in a short-term of one week after splenectomy but significantly improved in a long-term of one year after splenectomy. Additionally, compared to that before splenectomy, the esophageal gastric varices in most patients significantly improved one year after splenectomy. Thus, we may conclude that splenectomy is a safe and effective therapeutic measure for hypersplenism in WD patients who had been preoperatively treated with DMPS for powerful anti-copper therapy.