Takeuchi H, Mizuno T, Zhang G, Wang J, Kawanokuchi J, Kuno R, Suzumura A
J Biol Chem 2005 Mar 18;280(11):10444-54
Nagoya University Research Institute of Environmental Medicine, Department of NeuroImmunology, Nagoya 464-8601
Recent studies suggest that ExcitoToxicity may contribute to Neuronal damage in NeuroDegenerative Diseases including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis.
Activated Microglia have been observed around degenerative Neurons in these diseases, and they are thought to act as Effector Cells in the degeneration of Neural Cells in the Central Nervous System.
Neuritic Beading, focal bead-like swellings in the Dendrites and Axons, is a NeuroPathological Sign in Epilepsy, Trauma, Ischemia, Aging and NeuroDegenerative Diseases.
Previous reports showed that Neuritic Beading is induced by various stimuli including Glutamate or Nitric Oxide and is a Neuronal response to harmful stimuli.
However, the precise physiologic significance of Neuritic beading is unclear.
We provide evidence that Neuritic Beading induced by activated Microglia is a feature of Neuronal Cell dysfunction toward Neuronal death.
And, the NeuroToxicity of activated Microglia is mediated through N-Methyl-D-Aspartate () Receptor signaling.
Neuritic beading occurred concordant with a rapid drop in IntraCellular ATP levels and preceded Neuronal death.
The actual Neurite beads consisted of collapsed CytoSkeletal proteins and motor proteins arising from impaired Neuronal transport secondary to cellular energy loss.
The drop in IntraCellular ATP levels was due to the inhibition of Mitochondrial respiratory chain complex IV activity downstream of NMDA receptor signaling.
Blockage of NMDA receptors nearly completely abrogated Mitochondrial dysfunction and NeuroToxicity.
Thus, Neuritic Beading induced by activated Microglia occurs through NMDA receptor signaling and represents Neuronal Cell Dysfunction preceding Neuronal death.
Blockage of NMDA receptors may be an effective therapeutic approach for NeuroDegenerative Diseases.
Hickman SJ, Miszkiel KA, Plant GT, Miller DH
NeuroRadiology 2005 Jan;47(1):51-5
Institute of Neurology, University College London, Department of NeuroInflammation, NMR Research Unit, Queen Square, London, WC1N 3BG, UK
Optic Nerve Sheath dilatation or Gadolinium-enhancement on Magnetic Resonance Imaging in acute Optic Neuritis have been previously reported but have been thought to be rare occurrences.
This study recruited 33 patients with acute Unilateral Optic Neuritis. All had their Optic Nerves imaged with fat-saturated Fast Spin-Echo (FSE) imaging, and 28 had imaging before and after triple-dose Gadolinium-enhanced fat-saturated T1-weighted imaging.
Follow-up imaging was performed on 20 patients (15 following Gadolinium). A dilated SubArachnoid Space at the anterior end of the symptomatic Optic Nerve on FSE imaging was seen in 15/33 cases.
In three of these cases, dilatation was visible on short-term follow-up. Optic Nerve sheath enhancement was seen in 21/28 cases acutely: seven at the anterior end of the lesion only, five at the posterior end only and nine at both ends.
Optic Sheath enhancement was seen in 13 patients on follow-up. This study suggests that Optic Nerve Sheath dilatation on FSE images and Optic Nerve Sheath enhancement on triple-dose Gadolinium-enhanced images are common findings in Acute Optic Neuritis.
Optic Nerve Sheath dilatation may be due to inflammation of the Optic Nerve, with its associated swelling, interrupting the communication between the SubArachnoid Space of the diseased Optic Nerve and the Chiasmal Cistern.
Optic Nerve Sheath enhancement suggests that Meningeal inflammation occurs in Optic Neuritis, in agreement with pathological studies of both Optic Neuritis and Multiple Sclerosis.
Gamma Knife Surgery For Trigeminal Neuralgia: Improved Initial Response With Two Isocenters And Increasing Dose
Alpert TE, Chung CT, Mitchell LT, Hodge CJ, Montgomery CT, Bogart JA, Kim DY, Bassano DA, Hahn SS
J NeuroSurg 2005 Jan;102 Suppl:185-8
Upstate Medical University, Department of Radiation Oncology and NeuroSurgery, Syracuse, New York 13210, USA
The authors sought to evaluate the initial response of Trigeminal Neuralgia (TN) to gamma knife surgery (GKS) based on the number of shots delivered and radiation dose.
Between September 1998 and September 2003, some 63 patients with TN refractory to medical or surgical management underwent GKS at Upstate Medical University.
Ten patients had Multiple Sclerosis and 25 patients had undergone prior invasive treatment. Gamma knife surgery was delivered to the Trigeminal Nerve Root entry zone in one shot in 27 patients or two shots in 36 patients.
The radiation dose was escalated to less than or equal to 80 Gy in 20 patients, 85 Gy in 21 patients, and greater than or equal to 90 Gy in 22 patients.
Pain before and after GKS was assessed using the Barrow Neurological Institute Pain Scale and the improvement score was analyzed as a function of dose grouping and number of shots.
Sixty patients were available for evaluation, with an initial overall and complete response rate of 90% and 27%, respectively.
There was a greater improvement score for patients who were treated with two shots compared with one shot, mean 2.83 compared with 1.72 (p < 0.001).
There was an increased improvement in score at each dose escalation level: less than or equal to 80 Gy (p = 0.017), 85 Gy (p < 0.001), and greater than or equal to 90 Gy (p < 0.001).
Linear regression analysis also indicated that there was a greater response with an increased dose (p = 0.021).
Patients treated with two shots were more likely to receive a higher dose (p < 0.001). There were no severe complications. Five patients developed mild facial numbness.
Gamma knife surgery is an effective therapy for TN. Initial response rates appear to correlate with the number of shots and dose.
Local Tissue Damage Assessed With Statistical Mapping Analysis Of Brain Magnetization Transfer Ratio: Relationship With Functional Status Of Patients In The Earliest Stage Of Multiple Sclerosis
Ranjeva JP, Audoin B, Van Au Duong M, Ibarrola D, Confort-Gouny S, Malikova I, Soulier E, Viout P, Ali-Cherif A, Pelletier J, Cozzone P
AJNR Am J NeuroRadiol 2005 Jan;26(1):119-27
UMR Centre National de la Recherche Scientifique, Centre de Resonance Magnetique Biologique et Medicale, No. 6612, Faculte de Medecine, Marseille, France
Background And Purpose
In the early stage of Multiple Sclerosis (MS), conventional MR imaging parameters such as T2 lesion load fail to explain the clinical status of patients.
In the present work, we aimed to determine the ability of Magnification Transfer Imaging to better reflect the relationship between local tissue damage and functional status of MS patients.
We performed a comparative statistical mapping analysis on Brain tissue Magnetization Transfer Ratio (MTR) data measured in 18 patients with Clinically Isolated Syndrome Suggestive of MS (CISSMS) and 18 matched control subjects.
In the patients with CISSMS, a pattern of significant low MTR values was observed in the White Matter, Corpus Callosum, Bilateral OccipitoFrontal Fascicles, Right Fornix, Right Parietal White Matter, External Capsule, Right Superior Longitudinal Fasciculus (SLF), Right Inferior Longitudinal Fasciculus, Optica Radiata, Parietal White Matter, Right Cingulum, Gray Matter, Bilateral Thalamus, Bilateral Caudate, Right Insula, and left Brodmann Area (BA) 8.
No correlation was found between local MTR decrease and Expanded Disability Status Scale score. Significant correlations between MTR and MS Functional Composite scores (Spearman rank test, P < .05) were observed in the left BA40, right SLF, Right Frontal White Matter, Splenium, and Anterior Corpus Callosum.
Local MTR values correlated with Paced Auditory Serial Addition Test scores in the left BA40, right BA4, right SLF, and Splenium.
Statistical mapping analysis of Brain MTR data provides valuable information on the relationship between the location of Brain tissue damage and its functional impact in patients with MS, even in the earliest stage of the disease.