Factors that may affect recurrence of trigeminal neuralgia after percutaneous balloon compression.

OBJECTIVE: To investigate the efficacy of percutaneous balloon compression of the Gasserian Ganglion (PCGG) in the treatment of trigeminal neuralgia(TN)and the influencing factors of recurrence after PCGG. METHODS: The clinical data of 221 patients with TN treated by PCGG were retrospectively analyzed and followed-up to explore the postoperative efficacy. RESULTS: There were 158 cases of immediate disappearance of pain and 59 cases of delayed pain disappearance in patients after one PCGG operation, for an overall efficacy rate of 98.2%. Forty-nine patients experienced recurrence of pain, for a recurrence rate of 22.6%, and average recurrence time of 18 months. The effective rate of medication in patients with recurrent trigeminal neuralgia is 85.7%.Univariate and multivariate logistic regression analyses showed that hypertension disease and delayed pain disappearance were independent factors for recurrence. The incidence of inhibitory reaction of the trigeminal nerve during the operation was 97.3%. The most common postoperative complications were facial numbness, masticatory-muscle weakness, tinnitus, diplopia and keratitis, which occurred at rates of 76.9%, 28.1%, 14.5%, 11.8% and 10.4%, respectively. All of the complications resolved within 3 years after PCGG. CONCLUSIONS: PCGG is a safe and effective surgical method for the treatment of TN. The pain in most patients disappeared after surgery, leaving sequelae such as facial numbness, masticatory-muscle weakness and tinnitus. The mean time to recurrence of postoperative pain was 18 months, with hypertension disease and delayed pain disappearance as associated factors.

Factors that may delay disappearance of trigeminal neuralgia after percutaneous balloon compression.

INTRODUCTION: We set out to explore the factors that may affect delayed disappearance (DD) of trigeminal neuralgia (TN) after percutaneous balloon compression (PBC). MATERIAL AND METHODS: PBC was undergone by 221 patients with TN (95 male, 126 female) aged 33-89 years (mean 65). Delayed disappearance after surgery occurred in 59 patients. Follow-up continued until pain disappeared. RESULTS: A total of 221 patients, with an overall effective rate of 98.19%, including 59 patients with DD (26.70%), 158 patients with non-DD (71.49%), and four patients without relief, were included in this study. The time of delayed disappearance ranged from two to 30 days after surgery, with an average of c.9 days. Factors related to delayed disappearance included symptom duration (≥ 8 years), history of radiofrequency thermocoagulation, diabetes mellitus, herpes zoster, pain involving V2, and non-pear-shaped balloon. These were independent influencing factors (p < 0.05). CONCLUSIONS: PBC is a safe and effective surgical method for treating TN. Delayed disappearance is a common phenomenon after surgery, and is influenced by many factors.

Late-Onset Leukodystrophy Mimicking Hereditary Spastic Paraplegia without Diffuse Leukodystrophy on Neuroimaging.

PURPOSE: Leukodystrophies are frequently regarded as childhood disorders, but they can occur at any age, and the clinical and imaging patterns of the adult-onset form are usually different from the better-known childhood variants. Several reports have shown that various late-onset leukodystrophies, such as X-linked adrenoleukodystrophy and Krabbe disease, may present as spastic paraplegia with the absence of the characteristic white matter lesions on neuroimaging; this can be easily misdiagnosed as hereditary spastic paraplegia. The objective of this study was to investigate the frequency of late-onset leukodystrophies in patients with spastic paraplegia. PATIENTS AND METHODS: We performed genetic analysis using a custom-designed gene panel for leukodystrophies in 112 hereditary spastic paraplegia-like patients. RESULTS: We identified pathogenic mutations in 13 out of 112 patients, including five patients with adrenomyeloneuropathy, three with Krabbe disease, three with Alexander disease, and two with cerebrotendinous xanthomatosis. In terms of clinical manifestations, in addition to spastic paraplegia, three adrenomyeloneuropathy probands also had adrenocortical insufficiency, two Alexander disease probands developed urinary retention, one CTX proband developed cataracts and chronic diarrhea and the other presented with chronic diarrhea and mild tendon xanthomatosis. None of the patients had evidence of diffuse leukodystrophy on neuroimaging. CONCLUSION: Patients with late-onset spastic paraplegia should be screened for underlying leukodystrophies, irrespective of the presence of additional complicating symptoms and neuroimaging abnormalities.

Suppression of miR-10a-5p in bone marrow mesenchymal stem cells enhances the therapeutic effect on spinal cord injury via BDNF.

BACKGROUNDS/AIMS: Brain-derived neurotrophic factor (BDNF) plays a primary role in the maturation, proliferation, and differentiation of neuronal cells, can induce bone-marrow-derived mesenchymal stem cells (MSCs) to differentiate into nerve cells. This study aims to explore whether regulation of BDNF through microRNAs (miRNAs) in MSCs may further enhance the therapeutic effect on spinal cord injury (SCI). METHODS: Bioinformatics analyses were done to predict miRNAs that target BDNF in MSCs. Dual-luciferase reporter gene assays were performed to verify the target relationship between microRNA and BDNF. We examined the mRNA and protein levels of BDNF in MSCs by RT-qPCR and Western blot, respectively. CCK 8 assay was chosen to assess cell viability. MSCs were transduced with miR-10a-5p-ASO, which were transplanted into rats that underwent SCI. The tissue integrity percentage, cavity volume, and Basso-Beattie-Bresnahan (BBB) scale were assessed. Neurofilament (NF) was detected using immunohistochemistry. Histological features of spinal cord tissues examined following HE staining. RESULTS: MiR-10a-5p inhibited protein translation of BDNF, through binding to the 3'-UTR of the BDNF. MSCs transduced with MiR-10a-5p-ASO further increased the tissue integrity percentage, decreased cavity volume, and enhanced the recovery of BBB score in SCI model rats, compared to control MSCs. CONCLUSION: Upregulation of BDNF by miR-10a-5p suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.

Induction Of XLF And 53BP1 Expression Is Associated With Temozolomide Resistance In Glioblastoma Cells.

INTRODUCTION: Glioblastoma (GBM) is the most commonly diagnosed primary brain tumor in adults. The 14.6 months median survival period of GBM patients is still palliative due to resistance to the first-line chemotherapeutic agent temozolomide (TMZ). METHODS: The cell growth inhibition effect was assessed using the SRB assay. The mRNA expression levels were examined using RT-qPCR. The protein expression levels were determined using Western blot analysis. The DNA repair by non-homologous end-joining (NHEJ) was quantified using NHEJ reporter assay. The TMZ-induced apoptosis was detected by the Caspase 3/7 activity kit. The DNA binding activity in cells was determined using chromatin fractionation assay. The 53BP1 inhibitor was identified using virtual screening followed by Western blot analysis. The synergy between TMZ and 53BP1 inhibitor in vivo was analyzed using a xenograft mouse model. RESULTS: We found that non-homologous end joining (NHEJ), which is one of the major DNA double-strand break repair pathways, participates in acquired TMZ-resistance in GBM. Canonical NHEJ key factors, XLF and 53BP1, are upregulated in TMZ-resistant GBM cells. Depletion of XLF or 53BP1 in TMZ-resistant cells significantly improve the potency of TMZ against GBM cell growth. Importantly, we identified a small molecule HSU2018 to inhibit 53BP1 at nanomolar concentration. The combination of HSU2018 and TMZ generates excellent synergy for cell growth inhibition in TMZ-resistant GBM cells and xenograft. CONCLUSION: Our data suggest that NHEJ is a novel mechanism contributing to TMZ-resistance, and its key factors may serve as potential targets for improving chemotherapy in TMZ-resistant GBM.

1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) Induces the Apoptosis of Dopaminergic Neurons via Oxidative Stress and Neuroinflammation.

Several in vitro studies have revealed the neurotoxicity of 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo). However, the underlying mechanism has not been completely elucidated, particularly in vivo. This study was designed to study the neurotoxicity of TaClo in vivo by stereotactically injecting TaClo into the striatum of Wistar rats. After the TaClo injections, rats were subjected to an open field test, and their distance travelled and tracks showed decreasing trends over time. The results of liquid chromatography-mass spectrometry analysis showed that the motor dysfunction of the TaClo-treated rats was accompanied by reduced dopamine levels in the striatum. Based on the diffusion tensor imaging data, the apparent diffusion coefficient of the nigrostriatal pathway was significantly increased, and subsequent histological staining revealed the demyelination of nigrostriatal fibres after the TaClo treatment. TaClo induced a loss of tyrosine hydroxylase-positive cells in the substantia nigra compacta. Regarding the underlying mechanism, TaClo caused oxidative stress in the nigrostriatal system by increasing the production of reactive oxygen species and reducing the mitochondria membrane potential. Meanwhile, the elevated expression of Iba-1, TNF-α, IL-6, Cox-2, and iNOS indicated microglial activation and a strong innate immune response in the nigrostriatal system. In addition, activated caspase-3 levels were increased. Thus, both mitochondrial impairments and the innate immune response are involved in TaClo-induced neurotoxicity.

Inhibition of Drp1 after traumatic brain injury provides brain protection and improves behavioral performance in rats.

The imbalance between mitochondrial fusion and fission has been implicated in cerebral ischemia and several neurodegenerative diseases. However, the role of mitochondrial fission in traumatic brain injury (TBI) remains poorly understood. Mitochondrial fission is mediated by dynamin-related protein 1 (Drp1), which is highly expressed in the nervous system. In the present study, we investigated the changes in Drp1 expression in the ipsilateral hippocampus of rats after TBI and the effects of Mdivi-1 (a selective inhibitor of Drp1) as a post-insult treatment for TBI. Our findings showed that the protein levels of Drp1 were increased at 6 h and peaked at 12 h post-TBI, but we did not observe Drp1 phosphorylation at Ser616, Ser637, Ser40 or Ser44 during this process. We examined the effect of Mdivi-1 on trauma-induced brain damage in both vitro and vivo. In cells, Mdivi-1 significantly attenuated H2O2-induced mitochondrial membrane potential (MMP) dissipation in PC-12 cells. Three days of Mdivi-1 treatment significantly reduced the cortical lesion volume, blood-brain barrier permeability, brain edema and oxidative stress. Mdivi-1 reduced activated caspase-3 release in the cortical border zone and hippocampal dentate gyrus three days after TBI. Furthermore, treatment with Mdivi-1 for 4 weeks rescued neurogenesis in DG and attenuated hippocampal atrophy. Regarding behavioral outcomes, Mdivi-1-treated TBI rats showed a significant improvement in water maze acquisition and retention compared with the saline-treated TBI rats. Moreover, Mdivi-1 treatment reduced anxiety-like behavior in an open-field test. Our results support the notion that Mdivi-1 provides brain protection and improves the behavioral performance in TBI rats.

Adult-onset Krabbe disease in two generations of a Chinese family.

BACKGROUND: Krabbe disease (KD) is a rare autosomal recessive lysosomal storage disorder caused by deficiency of the galactocerebrosidase (GALC) enzyme. The adult-onset KD is infrequent, and often presenting with slowly progressive spastic paraplegia. Herein, we describe a two-generation concomitant Chinese pedigree of adult-onset KD in which the proband presented with acute hemiplegia at onset. METHODS: We collected the clinical and neuroimaging data of the pedigree. GALC enzyme activity detection and gene analysis were performed to confirm the diagnosis. Moreover, we reviewed all studies available on PubMed to understand the correlationship between phenotype and genotype of the identified mutations. RESULTS: The proband presented with sudden-onset weakness of left limbs with selective pyramidal tract involvement on diffusion-weighted imaging (DWI) of brain MRI. The GALC enzyme activity of him was low, and the GALC gene analysis revealed compound heterozygous pathogenic mutations of c.1901T>C and c.1901delT. More interestingly, the homozygous c.1901T>C mutations were found in the proband's asymptomatic father and two paternal uncles. Meanwhile, the literature review revealed the c.1901T>C mutation was only found in the late-onset form of KD. CONCLUSIONS: These observations, combined with previous reports, indicate that KD should be considered in the adult patients presenting selective pyramidal tract impairment even with sudden onset.

The expression of SPARC in human intracranial aneurysms and its relationship with MMP-2/-9.

OBJECTIVE: SPARC is a key determinant of invasion and metastasis in some tumors, such as gliomas, melanomas and prostate tumors. SPARC can change the composition and structure of the matrix and promote angiogenesis; these effects are closely related to clinical stage and the prognosis of tumors such as meningiomas. However, little is known about the expression of SPARC in intracranial aneurysms. The goal of this study was to establish the role of SPARC in human intracranial aneurysms. METHODS: Thirty-one intracranial aneurysms were immunohistochemically stained for SPARC, MMP-2 and MMP-9. As controls, normal Circle of Willis arteries were similarly immunostained. All specimens were retrieved during autopsies and were embedded in paraffin. To evaluate the expression levels of SPARC, MMP-2 and MMP-9, western blotting was also performed in three available intracranial aneurysm specimens. The limited availability of fresh intracranial aneurysm tissue was the result of the majority of patients choosing endovascular embolization. RESULTS: The results showed that SPARC, MMP-2 and MMP-9 were strongly expressed in intracranial aneurysm tissues; however, these proteins were expressed minimally or not at all in normal Circle of Willis arteries. The western blot results showed that the expression levels of SPARC, MMP-2 and MMP-9 were significantly up-regulated in intracranial aneurysms relative to the expression levels in the normal Circle of Willis arteries. Data analysis showed that SPARC was significantly correlated with MMP-2 and MMP-9, also with age and risk factors but not with the Hunt-Hess grade or with sex. CONCLUSION: The results indicate that SPARC is widely expressed in human intracranial aneurysms, and its expression correlates with MMP-2 and MMP-9 expression, age and risk factors but not with the Hunt-Hess grade. The results of this study suggest that SPARC has a pathogenic role in the alteration of the extracellular matrix of intracranial arteries during aneurysm formation.

[Endovascular treatment of middle cerebral artery bifurcation aneurysms].

OBJECTIVE: To summarize the diagnosis and endovascular treatment of middle cerebral artery (MCA) bifurcation aneurysm. METHODS: Between January 2010 and June 2011, 32 patients with MCA bifurcation aneurysm underwent endovascular treatment. There were 12 males and 20 females, aged 49.5 years on average (range, 35-81 years). All patients had sudden headache, 2 cases had disturbance of consciousness and hemiplegia, and 22 cases had a history of hypertension. Before operation, 10 cases were classified as Hunt-Hess level I, 15 cases as level II, and 7 cases as level III; 24 cases were classified as Fisher level II and 8 cases as level III. The patients underwent coil embolization using single microcatheter in 16 cases, using double microcatheter in 7 cases, using balloon-assisted in 4 cases, using single stent in 4 cases, and using double stent in 1 case. RESULTS: The results of postoperative immediate digital subtraction angiography showed that 30 patients achieved dense embolization, and 2 patients using single microcatheter achieved approximated dense embolization. Among them, 18 cases suffered extensive subarachnoid hemorrhage, thus lumbar puncture continued drainage was performed for 3-7 days; the other 14 cases had little subarachnoid hemorrhage, lumbar puncture released hemorrhagic cerebrospinal fluid discontinuously, and after 1 week, head CT demonstrated that subarachnoid hemorrhage was significantly decreased. At 1 day after surgery, 2 patients had local cerebral ischemia; after Nimotop and other drugs were used for 1 week, the symptom was alleviative. All 32 patients were followed up 4 to 17 months. No aneurysm rupture and bleed occurred during follow-up; no other complications or sequelae was observed except for 3 cases of hemiparesis and 1 case of aphasia. The computed tomographic angiography examination showed no re-open of dense embolized aneurysm at 3, 6 months, and 1 year after surgery. CONCLUSION: As long as appropriate intervention treatment method is chosen, endovascular treatment of MCA bifurcation aneurysm is safe and effective.

Alternating hemiplegia of childhood in chinese following long-term treatment with flunarizine or topiramate.

OBJECTIVE: Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear. METHODS: Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated. RESULTS: Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy. CONCLUSIONS: The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Effects of the group II mGlu receptor agonist 2R,4R-APDC on dentate gyrus cell proliferation in the adult rat brain after diffuse brain injury.

OBJECTIVES: Diffuse brain injury (DBI) has been shown to increase the proliferation of granule cell precursors in the adult dentate gyrus (DG). However, the mechanism by which DBI-induced cell proliferation in the DG may enhance seizure susceptibility remains largely unknown. MATERIALS AND METHODS: Using bromodeoxyuridine (BrdU) immunohistochemistry, we examined the effects of group II metabotropic glutamate receptor (mGluR) agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), on cell proliferation in the DG after DBI. RESULTS: It has been found that 2R,4R-APDC significantly blocked DBI-induced increase in the number of BrdU-positive cells in the DG, especially in hilus. In addition, double-label immunofluorescence staining showed that treatment with APDC did not affect the differentiation of newborn cells into neurons or astrocytes. Taken together, our findings indicate that the activation of mGluR system may inhibit the DBI-induced cell proliferation in the DG, but not the differentiation of newborn cells. DISCUSSION: It is suggested that 2R,4R-APDC has potential neuroprotection via inhibiting the aberrant neurogenesis induced by DBI, which is an important pathological basis of seizure or other abnormalities following DBI.

Glycogen synthase kinase-3 and p38 MAPK are required for opioid-induced microglia apoptosis.

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. We previously reported that opioids inhibit cell growth and trigger apoptosis in lymphocytes. However, the underlying mechanism by which microglia apoptosis in response to opioids is not yet known. In this study, we show that morphine induces microglia apoptosis and caspase-3 activation in an opioid-receptor dependent manner. Morphine decreased the levels of microglia phosphorylated Akt (p-Akt) and p-GSK-3ß (glycogen synthase kinase-3 beta) in an opioid-receptor dependent manner. More interestingly, GSK-3ß inhibitor SB216763 significantly increases morphine-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. Moreover, co-treatment of microglia with SB216763 and morphine led to a significant synergistic effect on the level of phospho-p38 mitogen-activated protein kinase (MAPK). In addition, inhibition of p38 MAPK by its specific inhibitor SB203580 significantly inhibited morphine-induced apoptosis and caspase-3 activation. Taken together, our data clearly demonstrates that morphine-induced apoptosis in microglial cells, which is mediated via GSK-3ß and p38 MAPK pathways.

The dual role of tumor necrosis factor-alpha in the pathophysiology of spinal cord injury.

Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediators in spinal cord injury (SCI). However, the role of TNF-alpha in this process is still under debate due to conflicting evidence. Here, we utilized TNF-alpha transgenic (tg) rats and wild-type (wt) littermates to further investigate the role of TNF-alpha in SCI. We observed that, in the acute phase post-SCI (< or =3 days), TNF-alpha tg rats showed higher expression of TNF-alpha protein and more apoptotic cells in the spinal cord than wt rats, while in the chronic period (> or =7 days), TNF-alpha tg rats exhibited persistent baseline level of TNF-alpha protein, better tissue healing, and more activated astrocytes in the border of the lesion than wt rats. These data further demonstrate that TNF-alpha plays a dual role in SCI and its role probably depends on when it is released after SCI and on which cellular population it acts on.

Poly(ADP-ribose) signal in seizures-induced neuron death.

Poly(ADP-ribose) is found to be involved in many physiological or pathological processes. It is mainly modulated by poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG). Either PARP or PARG is associated with the neuronal death in a variety of neurodegenerative diseases. Cumulative data have suggested that poly(ADP-ribose) regulation might have a therapeutic value in neurotoxicity-induced neuron damage, probably due to the inhibition of apoptosis, suppressing of inflammation and activation of cell survival signaling. We hypothesize poly(ADP-ribose) play an important role in seizures-induced neuron death. Seizures can lead to neuron degeneration as for the exitotoxity of glutamate. Recently, it is indicated seizures also can trigger PARP activation. Further investigation is needed to determine whether poly(ADP-ribose) signal is a therapeutic target for seizures-induced injury.

Meningioma without dural attachment: case report, classification, and review of the literature.

BACKGROUND: The primary occurrences of meningiomas without attachment to the dura are rare. Clinical considerations and pathophysiologic mechanisms about these tumors have not been sufficiently explored, and a complete classification has not been accomplished. CASE DESCRIPTION: A 16-year-old adolescent boy presented with epileptic seizure for 9 years. Neurologic deficits were not found on admission. Magnetic resonance imaging revealed a 25 x 23-mm mass lesion without dural attachment located in the parietooccipital region. The tumor was iso-intense on T1-weighted and hyperintense on T2-weighted images, and became clearly and heterogenously enhanced with gadolinium. During surgery, a right parietooccipital craniotomy revealed the tumor was completely buried in the sulcus occipitalis anterior. Total removal of the tumor was accomplished. Histologic examination indicated that the lesion was an atypical meningioma. CONCLUSION: According to sites of the tumor, supratentorial meningiomas without dural attachment are classified into 5 varieties, and posterior fossa meningiomas without dural attachment into 4 categories. Except for intraventricular ones, meningiomas without dural attachment predominantly occur in males. The average age is about 20 years younger than that of meningiomas in general. Fibroblastic meningiomas constitute the major subtype. Intraparenchymal or subcortical meningiomas should be considered as one type, which may arise from arachnoid cells of the pia mater within brain sulcus.

Traumatic arteriovenous fistula of the superficial temporal artery.

Arteriovenous fistula of the scalp is relatively rare. The superficial temporal artery is particularly vulnerable to trauma due to its long and relatively exposed course in the scalp. We report a traumatic arteriovenous fistula of the superficial temporal artery treated by complete surgical excision and review the literature with regard to etiology, clinical manifestations, pathogenesis, diagnosis and management of these unusual lesions.

A five-generation family with occipital encephalocele.

This study reports a Chinese family that has suffered from occipital encephalocele over five generations with a pattern of autosomal dominant inheritance. There were 113 family members in this family, and 21 of them had an occipital subscalp encephalocele. The patients with the disease showed normal or nearly normal neurological function.

Clinical and EEG characteristics of benign rolandic epilepsy in Chinese patients.

We retrospectively evaluated the clinical and electroencephalogram (EEG) characteristics of benign rolandic epilepsy (BRE) in Chinese children. Two hundred and seventy-six patients with BRE were enrolled in this study. All patients had their first seizure between the ages of 3 and 12 years. 39.5% (109 cases) of patients ceased to have further BRE seizures by the age of 6 years, 93.1% (257 cases) recovered by the age of 12 years and 96.7% (267 cases) recovered by the age of 18 years. Two hundred and twenty-seven patients suffered only simple partial seizures, whereas 49 patients suffered generalized seizures from onset of BRE. The EEG scans of 239 patients showed repetitive diphasic spikes or sharp waves with high amplitude, which were most dominant in the central or centrotemporal areas. The spikes were confined to one hemisphere in 180 patients and occurred bilaterally in 59 patients. Ninety-eight patients were treated with antiepileptic drugs (AEDs): carbamazepine (CBZ) or valproate (VPA). The study showed that, in Chinese children, BRE is remarkably characteristic in its clinical and EEG presentation. Although BRE is usually benign in terms of ease of control with AEDs and spontaneous seizure remission, for those patients with a high frequency of seizures, AEDs should be prescribed positively.