In vivo effects of antibodies from patients with anti-NMDA receptor encephalitis: further evidence of synaptic glutamatergic dysfunction

Background: A severe encephalitis that associates with auto-antibodies to the NR1 subunit of the NMDA receptor (NMDA-R) was recently reported. Patients' antibodies cause a decrease of the density of NMDA-R and synaptic mediated currents, but the in vivo effects on the extracellular glutamate and glutamatergic transmission are unknown. Methods. We investigated the acute metabolic effects of patients' CSF and purified IgG injected in vivo. Injections were performed in CA1 area of Ammon's horn and in premotor cortex in rats. Results: Patient's CSF increased the concentrations of glutamate in the extracellular space. The increase was dose-dependent and was dramatic with purified IgG. Patients' CSF impaired both the NMDA- and the AMPA-mediated synaptic regulation of glutamate, and did not affect the glial transport of glutamate. Blockade of GABA-A receptors was associated with a marked elevation of extra-cellular levels of glutamate following a pretreatment with patients' CSF. Conclusion: These results support a direct role of NMDA-R antibodies upon altering glutamatergic transmission. Furthermore, we provide additional evidence in vivo that NMDA-R antibodies deregulate the glutamatergic pathways and that the encephalitis associated with these antibodies is an auto-immune synaptic disorder. © 2010 Manto et al; licensee BioMed Central Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Peningkatan Hasil Belajar Siswa Pada Konsep Organ Tubuh Manusia Melalui Model Pembelajaran Langsung Di Kelas IV SDN 02 Karamat

Penelitian ini bertujuan untuk meningkatkan hasil belajar siswa kelas IV SDN 02 Karamat melalui model pembelajaran langsung pada konsep organ tubuh manusia. Jumlah siswa sebanyak 16 orang. Pelaksanaan penelitian tindakan kelas ini mengikuti tahap. Model penelitian ini mengacu pada modifikasi diagram yang dikemukakan oleh Kemmis dan Mc. Taggart, yaitu 1) Perencanaan tindakan, 2) Pelaksanaan tindakan, 3) Observasi, dan 4) Refleksi. Teknik pengumpulan data yang digunakan adalah lembar observasi guru dan siswa, LKS, serta tes hasil belajar siswa. Analisis data terdiri dari analisis data kualitatif dan data kuantitatif. Hasil penelitian menunjukkan bahwa terjadi peningkatan hasil belajar, dari siklus I ke siklus II. Hasil penelitian pada siklus I menunjukkan aktivitas guru rata-rata sangat baik dan aktivitas siswa rata-rata baik, serta persentase ketuntasan klasikal sebesar 69% dan daya serap klasikal 71%. Pada siklus II, penilaian aktivitas guru rata-rata sangat baik dan siswa rata-rata dalam kriteria baik, serta diperoleh ketuntasan klasikal 81% dan dan daya serap klasikal sebesar 77%. Hasil tersebut secara keseluruhan telah mencapai daya serap individu 65%, ketuntasan klasikal 80%, dan daya serap klasikal sebesar 65%. Dengan demikian, penerapan model pembelajaran langsung pada konsep organ tubuh manusia dapat meningkatkan hasil belajar siswa kelas IV SDN 02 Karamat

Immune-mediated cerebellar ataxias : clinical diagnosis and treatment based on immunological and physiological mechanisms

Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers

Efektivitas Mirror Therapy terhadap Kemampuan Bicara Pasien Pasca Stroke dengan Afasia Motorik

Kerusakan otak yang disebabkan stroke dapat menunjukkan geala secara permanen seperti kesulitan berbicara atau afasia motoric. Latihan gerakan lidah, bibir dan mengucapkan kata-kata didepan cermin adalah salah satu terapi yang dapat dilakukan. Tujuan penelitian ini adalah untuk mengetahui efektivitas mirror therapy terhadap kemampuan bicara pasien pasca stroke dengan afasia motorik di Poli Saraf RSUD. Dr.H. Moch Ansari Saleh Banjarmasin. Desain penelitian quasi experiment dengan one group pretest posttest design yang dilakukan selama 2 minggu dengan 6 kali digunakan dalam penelitian ini. Sampel dalam penelitian ini sebanyak 15 responden yang diambil dengan teknik purposive sampling. Selain kaca, instrument Derby Functional Communication Scale (DFCS) digunakan dalam penelitian ini. Hasil penelitian didapatkan perbedaan nilai tingkat kemampuan bicaranya yang signifikan sebelum (nilai = 8,73) dan sesudah perlakukan (nilai= 18,67). Hasil uji paired t-test diperoleh nilai p-value 0,000 < α 0,05. Simpulan dalam penelitian ini yaitu terdapat efektivitas penggunaan mirror therapy terhadap kemampuan bicara pasien pasca stroke dengan afasia motoric

Diagnostic criteria for primary autoimmune cerebellar ataxia—guidelines from an international task force on immune-mediated cerebellar ataxias

Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications

Tremorgenesis: a new conceptual scheme using reciprocally innervated circuit of neurons

Neural circuits controlling fast movements are inherently unsteady as a result of their reciprocal innervation. This instability is enhanced by increased membrane excitability. Recent studies indicate that the loss of external inhibition is an important factor in the pathogenesis of several tremor disorders such as essential tremor, cerebellar kinetic tremor or parkinsonian tremor. Shaikh and colleagues propose a new conceptual scheme to analyze tremor disorders. Oscillations are simulated by changing the intrinsic membrane properties of burst neurons. The authors use a model neuron of Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (It), and GABA/glycine mediated chloride currents. Post-inhibitory rebound is taken into account. The model includes a reciprocally innervated circuit of neurons projecting to pairs of agonist and antagonist muscles. A set of four burst neurons has been simulated: inhibitory agonist, inhibitory antagonist, excitatory agonist, and excitatory antagonist. The model fits well with the known anatomical organization of neural circuits for limb movements in premotor/motor areas, and, interestingly, this model does not require any structural modification in the anatomical organization or connectivity of the constituent neurons. The authors simulate essential tremor when Ih is increased. Membrane excitability is augmented by up-regulating Ih and It. A high level of congruence with the recordings made in patients exhibiting essential tremor is reached. These simulations support the hypothesis that increased membrane excitability in potentially unsteady circuits generate oscillations mimicking tremor disorders encountered in daily practice. This new approach opens new perspectives for both the understanding and the treatment of neurological tremor. It provides the rationale for decreasing membrane excitability by acting on a normal ion channel in a context of impaired external inhibition

Early detection of poor glycemic control in patients with diabetes mellitus in sub-Saharan Africa: a cohort study in Mozambique

Introduction: WHO estimates 422 million cases of diabetes mellitus worldwide. Mozambique has the second-highest mortality related to DM in the African region. Objectives of the present study are to provide data about a DM care service in Mozambique and to evaluate early outcomes of treatment. Methods: The new patients diagnosed with DM in a two-years period in a health centre in Maputo (Mozambique) were included in a retrospective cohort study. Fasting blood glucose (FBG), waist circumference (WC) and BMI were collected at baseline and after three months. Results: 188 patients were enrolled. Median BMI, WC and FBG at baseline were respectively 28 kg/m2(Inter Quartile Range [IQR]23.4-31.8), 98cm (IQR 87-105) and 209mg/dL (IQR 143-295). A non-pharmacological intervention was prescribed for six patients, while 182 patients received metformin 500 mg b.i.d. FBG was significantly reduced at control (226[±103.7]mg/dL vs 186[±93.2]mg/dL, p&lt;0.000); however, glycemic control was reached in 74 patients (39.4%); not controlled patients changed regimen. Elderly patients had a higher glycemic control (adjusted Odds Ratio 2.50, 95% CI 1.11-5.06, p=0.002). Conclusion: Strategies for early detection of scarce glycemic control are feasible in Mozambique and could lead to prompt regimen switch; an invasive therapeutic approach could be preferable in selected cases to achieve control

Cerebellar induced differential polyglot aphasia: a neurolinguistic and fMRI study

Research has shown that linguistic functions in the bilingual brain are subserved by similar neural circuits as in monolinguals, but with extra-activity associated with cognitive and attentional control. Although a role for the right cerebellum in multilingual language processing has recently been acknowledged, a potential role of the left cerebellum remains largely unexplored. This paper reports the clinical and fMRI findings in a strongly right-handed (late) multilingual patient who developed differential polyglot aphasia, ataxic dysarthria and a selective decrease in executive function due to an ischemic stroke in the left cerebellum. fMRI revealed that lexical-semantic retrieval in the unaffected L1 was predominantly associated with activations in the left cortical areas (left prefrontal area and left postcentral gyrus), while naming in two affected non-native languages recruited a significantly larger bilateral functional network, including the cerebellum. It is hypothesized that the left cerebellar insult resulted in decreased right prefrontal hemisphere functioning due to a loss of cerebellar impulses through the cerebello-cerebral pathways