Striatal parvalbumin interneurons are activated in a mouse model of cerebellar dystonia.

Dystonia is thought to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted an established cerebellar dystonia mouse model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe) and striatal neurons were activated in the model. Next, we examined whether administration of a dopamine D1 receptor agonist and dopamine D2 receptor antagonist or selective ablation of striatal parvalbumin (PV, encoded by Pvalb)-expressing interneurons could modulate the involuntary movements of the mice. The cerebellar dystonia mice had a higher number of cells positive for c-fos (encoded by Fos) in the EPN, SNr and GPe, as well as a higher positive ratio of c-fos in striatal PV interneurons, than those in control mice. Furthermore, systemic administration of combined D1 receptor agonist and D2 receptor antagonist and selective ablation of striatal PV interneurons relieved the involuntary movements of the mice. Abnormalities in the motor loop of the basal ganglia could be crucially involved in cerebellar dystonia, and modulating PV interneurons might provide a novel treatment strategy.

Cranial geometry in patients with dystonia and Parkinson's disease.

Abnormal skull shape has been reported in brain disorders. However, no studies have investigated cranial geometry in neurodegenerative disorders. This study aimed to evaluate the cranial geometry of patients with dystonia or Parkinson's disease (PD). Cranial computed tomography images of 36 patients each with idiopathic dystonia (IDYS), PD, and chronic subdural hematoma (CSDH) were analyzed. Those with IDYS had a significantly higher occipital index (OI) than those with CSDH (p = 0.014). When cephalic index (CI) was divided into the normal and abnormal groups, there was a significant difference between those with IDYS and CSDH (p = 0.000, α = 0.017) and between PD and CSDH (p = 0.031, α = 0.033). The age of onset was significantly correlated with the CI of IDYS (τ = - 0.282, p = 0.016). The Burke-Fahn-Marsden Dystonia Rating Scale motor score (BFMDRS-M) showed a significant correlation with OI in IDYS (τ = 0.372, p = 0.002). The cranial geometry of patients with IDYS was significantly different from that of patients with CSDH. There was a significant correlation between age of onset and CI, as well as between BFMDRS-M and OI, suggesting that short heads in the growth phase and skull balance might be related to the genesis of dystonia and its effect on motor symptoms.

Differences in amyloid-ß and tau/p-tau deposition in blood-injected mouse brains using micro-syringe to mimic traumatic brain microhemorrhages.

BACKGROUND: Cerebral microbleeds (CMBs) due to traumatic brain injuries (TBI) have been shown to lead to cognitive decline and impairment. CMBs caused by TBI may be associated with pathophysiological mechanisms involving inflammation and the accumulation of amyloid-ß (Aß), tau, and phosphorylated tau (p-tau), contributing to cognitive abnormalities. However, their relationships remain unclear. OBJECTIVES: To test our hypothesis that Aß, tau, and p-tau are accumulated and regulated separately in mice with injuries imitating CMBs from TBI, we studied. METHODS: Seven-week-old C57BL/6 male mice were injected with 15 µL of heparinized autologous blood or saline by micro-syringe into the front lobe. Expression profiles and regulation of Aß, tau, and p-tau were assessed immunohistochemically over time. RESULTS: On day 7 after blood injection, Iba-1+ and S100B+ cells in damaged cortex adjacent to the injection site were higher than saline injection group and non-injected sham. On days 3-14, Aß deposition were gradually increased but normalized by day 28. In contrast, tau/p-tau deposition gradually increased during days 14-28 and dispersed along the corticomedullary junction adjacent to hem deposits, indicating different expression profiles from Aß. Deposits of Aß, but not tau/p-tau, were phagocytosed by CD163+ macrophages increased by Gc-protein macrophage-activating factor during days 7-28, suggesting different mechanisms of deposition and regulation between Aß and tau/p-tau. CONCLUSION: Deposition and regulation differ between Aß and tau/p-tau in mice with injuries mimicking CMBs from TBI. Further clarification of relationships between the pathologies of cognitive impairment and their neurodegenerative consequences is needed.

Obsessive-compulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia.

We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ρ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.

Quantitative investigation of CeO2 surface proton conduction in H2 atmosphere.

This report is the first describing a study quantitatively analysing aspects of oxide surface protonics in a dry H2 atmosphere. Elucidating surface protonics is important for electrochemical and catalytic applications. In this study, AC impedance spectroscopy was used to investigate surface conduction properties of porous CeO2 at low temperatures (423-573 K) and in a dry H2 atmosphere. Results demonstrated that the conductivity increased by several orders of magnitude when H2 was supplied. Dissociative adsorption of H2 contributes to conduction by forming proton-electron pairs. Also, H/D isotope exchange studies confirmed protons as the dominant conduction carriers. Furthermore, H2 adsorption equilibrium modelling based on the Langmuir mechanism was applied to explain the H2 partial pressure dependence of conductivity. For the first time, the obtained model explains the experimentally obtained results both qualitatively and quantitatively. These findings represent new insights into surface protonics in H2 atmosphere.

Reversible Adsorption of Polycarboxylates on Silica Fume in High pH, High Ionic Strength Environments for Control of Concrete Fluidity.

Polycarboxylate-based superplasticizers are essential for production of ultrahigh-performance concrete (UHPC), facilitating particle dispersion through electrostatic repulsion and steric hindrance. This study examines for the first time the effect of changes in pH, ionic strength, and charge on the adsorption/desorption behavior of a polycarboxylate-based superplasticizer on silica fume in aqueous chemistries common in low-CO2 UHPC. Data from total organic carbon measurements, Fourier transform infrared and nuclear magnetic resonance spectroscopy, and zeta potential measurements reveal the silica surface chemistry and electrokinetic properties in simulated UHPC. Addition of divalent cations (Ca2+) results in polycarboxylate adsorption on silica fume via (i) adsorption of Ca2+ ions on the silica surface and a negative zeta potential of lower magnitude on the silica surface and (ii) reduction of polycarboxylate anionic charge density due to complexation with Ca2+ ions and counter-ion condensation. Addition of OH- ions results in polycarboxylate desorption via deprotonation of silanol groups and a negative zeta potential of greater magnitude on the silica surface. Simultaneous addition of both Ca2+ and OH- results in rapid polycarboxylate desorption via (i) formation of an electric double layer and negative zeta potential on the silica surface and (ii) an increase in polycarboxylate anionic charge density due to deprotonation of the carboxylate groups in the polymer backbone, complexation with Ca2+ ions, and counter-ion condensation. This provides an explanation for the remarkable fluidizing effect observed upon addition of small amounts (1.0 wt %) of a solid, powdered Ca source to fresh, low-CO2, UHPC, which exhibits significantly higher fresh state pH (>13) than those based on Portland cement (pH 11).

Chronic subdural hematoma associated with dural metastasis leads to early recurrence and death: A single-institute, retrospective cohort study.

The prevalence of chronic subdural hematoma (CSDH) associated with dural metastasis is uncertain, and appropriate treatment strategies have not been established. This study aimed to investigate the characteristics of and appropriate treatment strategies for CSDH associated with dural metastasis. We retrospectively reviewed the charts of 214 patients who underwent surgery for CSDH. The patients were divided into the dural metastasis group (DMG; n = 5, 2.3%) and no dural metastasis group (No-DMG; n = 209, 97.3%). Patient characteristics, treatment, and outcomes were compared between the two groups. Active cancer was detected in 31 out of 214 patients, 5 of whom (16.1%) had dural metastasis. In-hospital death (80.0% vs. 0%; p < 0.001) and recurrence within 14 days (80.0% vs. 2.9%; p < 0.001) and 60 days (80.0% vs. 13.9%; p = 0.002) were significantly prevalent in the DMG. All patients in the DMG developed subdural hematoma re-accumulation requiring emergent surgery because of brain herniation, and patients in the DMG had significantly worse recurrence-free survival (p < 0.001). This relationship remained significant (p < 0.001) even when the analysis was limited to the active cancer cohort (n = 31). CSDH associated with dural metastasis leads to early recurrence and death because of the difficulty in controlling subdural hematoma re-accumulation by common drainage procedures. Depending on the primary cancer status, withdrawal of active treatment and change to palliative care should be discussed after diagnosing CSDH associated with dural metastasis.

Ataxia with vitamin E deficiency in the Philippines†: A case report of two siblings.

Here we report two siblings with ataxia and peripheral neuropathy. One patient showed head tremors. Genetic analysis revealed a mutation in the hepatic α-tocopherol transfer protein (α-TTP) gene (TTPA) on chromosome 8q13. They were diagnosed with ataxia with vitamin E deficiency which is firstly reported in the Philippines. As the symptoms of ataxia with vitamin E deficiency can be alleviated with lifelong vitamin E administration, differential diagnosis from similar syndromes is important. In addition, ataxia with vitamin E deficiency causes movement disorders. Therefore, a common hereditary disease in the Philippines, X-linked dystonia-parkinsonism, could be another differential diagnosis. The Philippines is an archipelago comprising 7,107 islands, and the prevalence of rare hereditary diseases among the populations of small islands is still unclear. For neurologists, establishing a system of genetic diagnosis and counseling in rural areas remains challenging. These unresolved problems should be addressed in the near future. J. Med. Invest. 68 : 400-403, August, 2021.

Dystonia and Cerebellum: From Bench to Bedside.

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions.

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia.

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% (p < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.

Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components.

The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery.

First observation of surface protonics on SrZrO3 perovskite under a H2 atmosphere.

This is the first direct observation that surface proton hopping occurs on SrZrO3 perovskite even under a H2 (i.e. dry) atmosphere. Understanding proton conduction mechanisms on ceramic surfaces under a H2 atmosphere is necessary to investigate the role of proton hopping on the surface of heterogeneous catalysts in an electric field. In this work, surface protonics was investigated using electrochemical impedance spectroscopy (EIS). To extract the surface proton conduction, two pellets of different relative densities were prepared: a porous sample (R.D. = 60%) and a dense sample (R.D. = 90%). Comparison of conductivities with and without H2 revealed that only the porous sample showed a decrease in the apparent activation energy of conductivity by supplying H2. H/D isotope exchange tests revealed that the surface proton is the dominant conductive species over the porous sample with H2 supply. Such identification of a dominant conductive carrier facilitates consideration of the role of surface protonics in chemical reactions.

Effects of metal cation doping in CeO2 support on catalytic methane steam reforming at low temperature in an electric field.

Catalytic methane steam reforming was conducted at low temperature using a Pd catalyst supported on Ce1-x M x O2 (x = 0 or 0.1, M = Ca, Ba, La, Y or Al) oxides with or without an electric field (EF). The effects of the catalyst support on catalytic activity and surface proton hopping were investigated. Results show that Pd/Al-CeO2 (Pd/Ce0.9Al0.1O2) showed higher activity than Pd/CeO2 with EF, although their activity was identical without EF. Thermogravimetry revealed a larger amount of H2O adsorbed onto Pd/Al-CeO2 than onto Pd/CeO2, so Al doping to CeO2 contributes to greater H2O adsorption. Furthermore, electrochemical conduction measurements of Pd/Al-CeO2 revealed a larger contribution of surface proton hopping than that for Pd/CeO2. This promotes the surface proton conductivity and catalytic activity during EF application.

[A Case of Spontaneous Intracranial Hypotension Successfully Treated with Repetitive Epidural Blood Patch after Warfarin Reversal].

We report a case of spontaneous intracranial hypotension successfully treated with repetitive epidural blood patch after warfarin reversal. A 75-year-old man presented with a 2-week history of headache. He was being treated with warfarin for atrial fibrillation. Neurological examination on admission showed mild disorientation. Prothrombin time-international normalized ratio(PT-INR)was elevated to 2.43. Initial magnetic resonance images of the brain demonstrated bilateral subdural hematomas, distortion of midbrain and diffuse pachymeningeal enhancement. Conservative treatments with bed rest and hydration were administered. On the third posthospital day, he became lethargic and emergently underwent epidural blood patch(EBP)at lumbar level. Consciousness disturbance improved immediately but reappeared 12 hours after the EBP. The second EBP was performed but consciousness level decreased again 12 hours later. The effect of warfarin was reversed by administration of vitamin K and fresh frozen plasma before the third EBP. After the procedure, he became alert. The findings of neurological examination did not change but a CT on day 12 revealed increase in volume of left-sided subdural hematoma. He underwent EBP and evacuation of hematoma. The neurological findings remained unchanged. A CT on the 17th posthospital day showed increase of right-sided subdural hematoma, and EBP and evacuation of hematoma were then performed. After the 5th EBP, the clinical course was uneventful. Predictors for successful EBP are not fully clarified. In patients who undergo anticoagulation therapy, EBP may be ineffective and normalization of coagulability required.

Mass on the head : Spontaneous arteriovenous fistula of the superficial temporal artery.

An arteriovenous fistula of the superficial temporal artery (STA) is a direct and abnormal communication between the STA, feeding artery, and superficial temporal vein, draining veins that bypass the capillary network. Several cases of trauma-induced or iatrogenic-induced arteriovenous fistula (AVF) of the STA have been reported ; however, spontaneous AVF of the STA not associated with trauma or medical treatment are extremely rare. Herein, we present a case of spontaneous AVF of the STA diagnosed in old age. J. Med. Invest. 66 : 209-210, February, 2019.

[Cerebral Venous Sinus Thrombosis Following Cisplatin-Based Chemotherapy for Testicular Tumor].

A man in his 30s who presented with an enlarged right testicle was diagnosed with a germ cell tumor via orchiectomy. Adjuvant chemotherapy with cisplatin, etoposide and bleomycin(BEP)was initiated. He developed a headache 8 days later, followed by neurological deficits 10 days later. Magnetic resonance imaging(MRI)and magnetic resonance venography(MRV)showed thrombotic occlusion at the superior sagittal sinus. Anticoagulant therapy with heparin was initiated. However, a generalized epileptic seizure occurred 11 days later, and an antiepileptic drug therapy was initiated. The headache and neurological deficits gradually improved, and MRI findings showed that the superior sagittal sinus had re-canalized. The main cause of the sinus thrombosis in this patient was considered dehydration and cisplatin-induced hypercoagulability. Five courses of BEP therapy were carried out with care to avoid dehydration. The patient has remained free of testicular tumor recurrence, metastasis, and cerebral sinus thrombosis for 2 years. Cisplatin-based chemotherapy is an established risk factor for venous thromboembolism(VTE), and cerebral sinus thrombosis is a rare but dangerous complication. Therefore, cerebral sinus thrombosis should be considered when patients with testicular cancer who undergo cisplatin-based chemotherapy start to develop neurological symptoms. Clinicians should be aware of this treatable complication.