Cervical Cord Lesions Research Articles

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

Transcranial magnetic stimulation (TMS) is an electrophysiological technique used to elicit motor evoked potentials (MMEPs) to evaluate the functional integrity of the descending motor fibres in the spinal cord. Successful application of the technique was reported in horses with spinal cord compression. However, limited data are available on the correlation of TMS with histopathological changes. To determine sensitivity of TMS for assessing the integrity of the spinal cord in horses with compressive lesions of the spinal cord. Case series. The study was conducted on 6 horses with spinal ataxia grade III-V/V admitted to the Faculty of Veterinary Medicine, Ghent University. The horses underwent TMS, radiography of the cervical or thoracolumbar vertebral column, and myelography (4/6). All horses were subjected to euthanasia and the spinal cord examined histopathologically. In 5/6 horses MMEPs with abnormal onset latencies in both extensor carpi radialis muscles and cranial tibialis muscles were recorded, suggesting a cervical spinal cord lesion. Radiography revealed cervical vertebral malformation (4/5) with cervical vertebral canal stenosis (3/5) and tumour/osteomyelitis (1/5). In 1/6 horse MMEPs with normal onset latencies in extensor carpi radialis muscles and prolonged onset latencies in tibialis cranialis muscles were recorded, suggesting a thoracolumbar spinal cord lesion. Radiography revealed deformation of the 7th and 8th thoracic vertebrae. Myelography showed reduction in dural diameter and dorsal contrast column (4/4). Histopathological examination of the spinal cord confirmed compressive type lesions in all 6 horses with degenerative changes in the white matter of all funiculi, ballooning of myelin sheets, swollen axons, loss of axons and astroglial activation. In this case series abnormal function of descending motor pathways as registered by TMS showed 100% sensitivity with the histopathological characteristics of compressive lesions in the spinal cord, but the number of horses is limited and further research is warranted. Ethical animal research: Research ethics committee oversight not currently required by this conference: the study was performed on material collected during clinical procedures. Explicit owner informed consent for participation in this study was not stated. Not applicable. Competing interests: None declared.

Unraveling the neuroimaging predictors for motor dysfunction in long-standing multiple sclerosis.

To find the strongest neuroimaging predictors for motor dysfunction using conventional and quantitative imaging measures focusing on the corticospinal tract (CST) in a large cohort of patients with long-standing multiple sclerosis (MS). In this cross-sectional study, a wide spectrum of neuroimaging measures at the whole-brain, cervical, and CST level were analyzed in 195 patients with MS and 54 healthy controls. Motor function was assessed using the Expanded Disability Status Scale (EDSS), 9-Hole Peg Test, Timed 25-Foot Walk Test, and Multiple Sclerosis Walking Scale. Associations between damage in different parts of the motor system and motor functioning were assessed using stepwise linear regression. Patients had an average disease duration of 19.98 (±6.99) years and a median EDSS score of 4 (range: 1.0-8.0). EDSS score was associated with number of infratentorial and cervical cord lesions, lesion volume in the CST, and mean upper cervical cord area (adjusted R(2) = 0.403). Timed 25-Foot Walk Test score was associated with number of infratentorial lesions and cerebellar volume (adjusted R(2) = 0.150), 9-Hole Peg Test score with number of infratentorial lesions and thickness of the cortex connected to the CST (adjusted R(2) = 0.245), and Multiple Sclerosis Walking Scale with number of infratentorial and cervical lesions, thickness of the cortex connected to the CST, and mean upper cervical cord area (adjusted R(2) = 0.354). Motor dysfunction in MS has a complex substrate that cannot be ascribed to a single neuroimaging finding, but is the consequence of infratentorial and spinal cord damage, as well as damage in the CST.

Longitudinal ultra-extensive transverse myelitis as a manifestation of neurosarcoidosis

ObjectiveTo analyze the clinical characteristics and outcome of patients with neurosarcoidosis manifesting as longitudinal transverse myelitis spanning 6 or more spinal segments. MethodRetrospective analysis of 7 cases from a single institution. ResultsFour males and 5 African–American were included. The mean onset age for neurological symptoms was 49.1years old. Only 1 patient had a prior diagnosis of sarcoidosis. In all patients, spinal MRI showed contiguous cervical and/or thoracic cord lesions predominantly in a central or centrodorsal location, associated with parenchymal or leptomeningeal gadolinium enhancement. Cerebral spinal fluid (CSF) pleocytosis was present in all and hypoglycorrhachia in 3 patients. Angiotensin-converting enzyme (ACE) level was elevated in the serum of 1 patient while being normal in the CSF of all 4 cases tested. Chest imaging facilitated the diagnosis of sarcoidosis in all cases. The use of corticosteroid and immunosuppressive agents including infliximab and methotrexate led to improved outcome. ConclusionsNeurosarcoidosis should be considered in the differential diagnosis of longitudinal ultra-extensive myelitis, even in the absence of previously diagnosed sarcoidosis. Timely usage of corticosteroid and immunosuppressive agents improves the clinical outcome of patients with ultra-extensive spinal cord sarcoidosis.

Thoracic spinal cord lesions are influenced by the degree of cervical spine involvement in multiple sclerosis.

Cross-sectional analyses. To determine whether cervical spinal cord lesions predict the presence of thoracic cord lesions in multiple sclerosis (MS) patients. Single MS Clinic, AZ, USA. All MS patients, with MRI studies of the brain, cervical and thoracic spine obtained during a single scanning session, were acquired during a 1-year period. Clinical, demographic and imaging covariates were used in a multivariate regression model to refine predictors of thoracic cord involvement. A total of 687 patients were evaluated, and patients were excluded because of a diagnosis of other neurological disorders, not meeting the 2010 McDonald criteria for MS (n=222) or incomplete neuraxis imaging (n=339). The study cohort comprised 126 patients. There was an increase in the odds ratio (OR) of thoracic spine involvement when any cervical spine lesion was present (OR=6.08, 95% confidence interval (2.21-16.68), P<0.001). The multivariate logistic regression model demonstrated a substantial and significant increase in the odds of thoracic spine involvement when more than two cervical spine lesions were present, two lesions (OR 4.44, (0.91-21.60), P=0.06), three lesions (OR 19.76, (3.51-111.17), P=0.001), four or more lesions (OR 20.49, (1.97-213.23), P=0.012) and diffuse lesions (OR 71.94, (5.28-979.88), P=0.001), when adjusting for significant covariates including clinical symptoms, brain lesions, disease duration and treatment exposure. Thoracic spinal cord lesions appear to be predicated on the degree of cervical spine involvement in patients with MS, a risk that appears to be independent of brain findings or clinical features.

Surgical Outcomes of High-Grade Spinal Cord Gliomas.

Study DesignA retrospective study.PurposeThe purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas.Overview of LiteratureThe optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma.MethodsWe analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test.ResultsNone of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03).ConclusionsThe surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival.

10. Disseminated oligodendroglial-like leptomeningeal tumour of childhood: a case series of a rare and newly described entity

Background Disseminated oligodendroglial-like leptomeningeal tumour of childhood (DOLTC) is a newly described, rare paediatric neoplasm characterised by dissemination of oligodendroglial-like neoplastic cells in the central nervous system surface and leptomeninges. Aim To compare the clinicopathological features of cases of DOLTC diagnosed and treated at the Royal Children's Hospital, Melbourne, with those previously reported. Methods A retrospective review was performed of all cases of DOLTC diagnosed and treated at the Royal Children's Hospital, Melbourne. Results Three cases of DOLTC were identified, two were female and one male. The age range at presentation was 3–14 years. Presentating symptoms included acute unilateral cranial nerve palsy, symptoms of raised intracranial pressure and of spinal cord compression. MRI brain and spine revealed hydrocephalus and marked basal brain and extensive spinal leptomeningeal enhancement in all cases, and an intramedullary C6–7 enhancing cervical cord lesion in two cases. In all three cases meningeal biopsy revealed infiltration of leptomeninges by sheets of round cells with small regular nuclei and clear cytoplasm which were GFAP and synaptophysin positive. One case had focal histological features resembling pilocytic atrocytoma and in another case the infiltrating round cells were scattered and subtle, and detected only after examining multiple levels. BRAF analysis was performed on two cases and revealed a BRAF-KIAA1549 fusion in one case. Conclusion Given the sometimes subtle histological features the diagnosis of DOLTC is aided by immunohistochemistry. This is the first series in which BRAF analysis was performed in DOLTC and the presence of the BRAF fusion (fBRAF) in one case extends the spectrum of tumour types associated with fBRAF to include this rare entity.

Cervical cord lesion load is associated with disability independently from atrophy in MS.

To investigate whether spinal cord (SC) lesion load, when quantified on axial images with high in-plane resolution, is associated with disability in multiple sclerosis (MS). Twenty-eight healthy controls and 92 people with MS had cervical SC 3T MRI with axial phase sensitive inversion recovery, T2, and magnetization transfer (MT) sequences. We outlined all visible focal lesions from C2 to C4 to obtain lesion load and also measured upper cervical cord area. We measured MT ratio in normal-appearing cord tissue and in lesions. Disability was recorded using the Expanded Disability Status Scale (EDSS) and MS Functional Composite. We used linear regression models to determine associations with disability. SC lesion load was significantly higher in both secondary progressive MS (SPMS) (p = 0.008) and primary progressive MS (PPMS) (p = 0.02) compared to relapsing-remitting MS (RRMS); in each comparison, adjustment was made for age, sex, and brain volume. These differences were not evident when EDSS was added as a covariate. SC area was significantly lower in both SPMS (p < 0.001) and PPMS (p = 0.009) compared to RRMS. In a multiple regression model, cord lesion load (p < 0.001), cord area (p = 0.003), age (p < 0.001), and sex (p = 0.001) were independently associated with EDSS (R(2) = 0.58). Cord lesion load (p = 0.003), cord area (p = 0.034), and brain parenchymal fraction (p = 0.007) were independently associated with the 9-hole peg test (R(2) = 0.42). When quantified on axial MRI with high in-plane resolution, upper cervical cord lesion load is significantly and independently correlated with physical disability and is higher in progressive forms of MS than RRMS.

Focal Hand Dystonia as a Sign of Demyelinating Attack in Multipl Sclerosis: 'Report of Three Cases’

Ad dress for Cor res pon den ce/Ya z›fl ma Ad re si: Ozge Ocek MD, Izmir Bozyaka Training and Research Hospital, Clinic of Neurology, Izmir, Turkey Phone: +90 232 342 66 60 E-mail: ozge_giray@yahoo.com Re cei ved/Ge lifl Ta ri hi: 28.09.2013 Ac cep ted/Ka bul Ta ri hi: 06.02.2014 Although it is known that dystonia is a basal ganglia disease, dystonic symptoms have been observed in association with lesions of various sites located in sensory and motor pathways. We report three cases of paroxysmal focal hand dystonia, which may be due to the damage of the somatosensorial pathways in the cervical spinal cord. We suggest that the dystonia in our patients may be related to these active demyelinating cervical plaques. Two female and one male patients with definite relapsing remitting Multiple sclerosis (MS) between the ages of 22 to 45 were admitted with serious disability while using their right hands. In all three cases abnormal posture in the right hand and involuntary sustained contractions together with minor choreiform movements of the fingers were observed. Cervical MRI showed contrast-enhancing demyelinating lesions at the level of C2-3 in all patients. One of the patient’s cranial MRI revealed also two new contrast-enhancing plaques on the neighbourhood of right posterior lateral ventricle and parietal cortex. No new or enhancing lesion was detected in the basal ganglia; indicating that the cervical spinal cord lesions were responsible for hand dystonia. In one of the patients, the right median somatosensory evoked potential response was absent in accordance with the clinical symptom. All three patients were treated with 1 gr. intravenous methylprednisolone per day for 5-10 days. Approximately one month later, clinical symptoms have been completely disappeared and control cervical MRI revealed resolution of the active lesions in all. (Turkish Journal of Neurology 2014; 20:141-143)

A Cost-Utility Analysis of Sacral Anterior Root Stimulation (SARS) Compared to Medical Treatment in Complete Spinal Cord Injured Patients with a Neurological Bladder.

 Main hypothesis of the model: patients capable of complete and voluntary micturition (CVM) under SARS no longer have urinary disorders. We thus identified three categories of patients in our model: 1) SARS capable of CVM (SARS success); 2) SARS incapable of CVM (SARS failure); 3) reference medical treatment. SARS patients incapable of CVM receive the reference medical treatment. Consequently, categories 2 and 3 experience the same progression in our model (figure 1).  Population: Theoretical cohorts of patients with a complete traumatic cervical or thoracic spinal cord lesion since ≥1 year, and suffering from a neurological bladder.  Outcome Measures: Effectiveness was expressed as quality adjusted life years (QALY). Costs were valued in EUR 2013 in the perspective of the French health system.

Vertebral artery dissection presenting as Brown Sequard syndrome

Vertebral artery dissection is an increasingly recognised cause of stroke in patients younger than 45 years. It closely resembles its sister condition, carotid artery dissection but its aetiology and presentation is unique. It may present commonly as infarction of posterior cranial fossa structures- brainstem, medulla, cerebellum. Here we report a rare case of Vertebral Artery Dissection in a young lady resulting in cervical cord lesion presenting as Brown Sequard Syndrome. The case is being reported because of its unusual and rare presentation. Copyright © 2014, Indian Journal of Medical Specialities. Published by Reed Elsevier India Pvt. Ltd. All rights reserved.

Mean upper cervical cord area (MUCCA) measurement in long-standing multiple sclerosis: Relation to brain findings and clinical disability

Background: The majority of patients with multiple sclerosis (MS) present with spinal cord pathology. Spinal cord atrophy is thought to be a marker of disease severity, but in long-disease duration its relation to brain pathology and clinical disability is largely unknown. Objective: Our aim was to investigate mean upper cervical cord area (MUCCA) in patients with long-standing MS and assess its relation to brain magnetic resonance imaging (MRI) measures and clinical disability. Methods: MUCCA was measured in 196 MS patients and 55 healthy controls using 3DT1-weighted cervical images obtained at 3T MRI. Clinical disability was measured using the Expanded Disability Status Scale (EDSS), Nine-Hole-Peg test (9-HPT), and 25 feet Timed Walk Test (TWT). Stepwise linear regression was performed to assess the association between MUCCA and MRI measures, and between MUCCA and clinical disability. Results: MUCCA was smaller (mean 11.7%) in MS patients compared with healthy controls (72.56±9.82 and 82.24±7.80 mm2 respectively; p<0.001), most prominently in male patients. MUCCA was associated with normalized brain volume, and number of cervical cord lesions. MUCCA was independently associated with EDSS, TWT, and 9-HPT. Conclusion: MUCCA was reduced in MS patients compared with healthy controls. It provides a relevant marker for clinical disability in long-standing disease, independent of other MRI measures.

Intraoperative changes in transcranial motor evoked potentials and somatosensory evoked potentials predicting outcome in children with intramedullary spinal cord tumors

Intraoperative dorsal column mapping, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) have been used in adults to assist with the resection of intramedullary spinal cord tumors (IMSCTs) and to predict postoperative motor deficits. The authors sought to determine whether changes in MEP and SSEP waveforms would similarly predict postoperative motor deficits in children. The authors reviewed charts and intraoperative records for children who had undergone resection for IMSCTs as well as dorsal column mapping and TcMEP and SSEP monitoring. Motor evoked potential data were supplemented with electromyography data obtained using a Kartush microstimulator (Medtronic Inc.). Motor strength was graded using the Medical Research Council (MRC) scale during the preoperative, immediate postoperative, and follow-up periods. Reductions in SSEPs were documented after mechanical traction, in response to maneuvers with the cavitational ultrasonic surgical aspirator (CUSA), or both. Data from 12 patients were analyzed. Three lesions were encountered in the cervical and 7 in the thoracic spinal cord. Two patients had lesions of the cervicomedullary junction and upper spinal cord. Intraoperative MEP changes were noted in half of the patients. In these cases, normal polyphasic signals converted to biphasic signals, and these changes correlated with a loss of 1-2 grades in motor strength. One patient lost MEP signals completely and recovered strength to MRC Grade 4/5. The 2 patients with high cervical lesions showed neither intraoperative MEP changes nor motor deficits postoperatively. Dorsal columns were mapped in 7 patients, and the midline was determined accurately in all 7. Somatosensory evoked potentials were decreased in 7 patients. Two patients each had 2 SSEP decreases in response to traction intraoperatively but had no new sensory findings postoperatively. Another 2 patients had 3 traction-related SSEP decreases intraoperatively, and both had new postoperative sensory deficits that resolved. One additional patient had a CUSA-related SSEP decrease intraoperatively, which resolved postoperatively, and the last patient had 3 traction-related sensory deficits and a CUSA-related sensory deficit postoperatively, none of which resolved. Intraoperative TcMEPs and SSEPs can predict the degree of postoperative motor deficit in pediatric patients undergoing IMSCT resection. This technique, combined with dorsal column mapping, is particularly useful in resecting lesions of the upper cervical cord, which are generally considered to be high risk in this population. Furthermore, the spinal cord appears to be less tolerant of repeated intraoperative SSEP decreases, with 3 successive insults most likely to yield postoperative sensory deficits. Changes in TcMEPs and SSEP waveforms can signal the need to guard against excessive manipulation thereby increasing the safety of tumor resection.

Intramedullary spinal cord mass presumptively associated with leishmaniasis in a dog

A 9-year-old male Miniature Poodle was evaluated because of progressive severe right hemiparesis, right forelimb lameness, and signs of cervical pain. A low body condition score (2/9) and popliteal lymphadenopathy were detected. Results of a CBC, serum biochemical analyses, urinalysis, cytologic examination of bone marrow and popliteal lymph node aspirates, and serum ELISA were consistent with systemic leishmaniasis. Magnetic resonance imaging of the cervical spinal cord revealed an intramedullary mass extending from the caudal aspect of the C5 vertebral body to the C5-6 intervertebral disk space with a contrast medium-enhanced pattern that had 3 zones (central contrast medium-enhanced core, intermediate isointense zone, and peripheral contrast medium-enhanced ring). Surgical biopsy of the mass was performed by means of a right C5-6 dorsal hemilaminectomy. Results of PCR assays for detection of Leishmania DNA in CSF and tissue biopsy samples were positive. Treatment for systemic leishmaniasis was initiated. Two months later, body condition, neurologic signs, and gait of the dog had substantially improved; the dog had mild right forelimb paresis at that time. Results of follow-up MRI indicated resolution of the cervical spinal cord lesion. Four months after diagnosis, the dog's neurologic condition was stable. To the authors' knowledge, this report is the first in which clinical findings, clinicopathologic data, and MRI characteristics of an intramedullary inflammatory spinal cord lesion presumptively attributable to leishmaniasis in a dog have been reported, and the first report of CNS leishmaniasis in a dog with MRI resolution and a successful clinical response to treatment.

A case of syncope due to prolonged sinus arrest in a patient with autonomic nervous dysfunction caused by cervical spinal cord lesion

A case of syncope due to prolonged sinus arrest in a patient with autonomic nervous dysfunction caused by cervical spinal cord lesion

Subtle Upper Limb Impairment In Radiological Isolated Syndrome Subjects

Objective: Spatial dissemination of focal white matter brain lesions, highly suggestive of multiple sclerosis (MS) in subjects without clinical neurological symptoms, is referred to as radiological isolated syndrome (RIS). The aim of this study was to demonstrate that kinematic parameters are able to measure motor performance and to identify subtle symptoms undetectable with the clinical examination. Methods: We investigated the clinical, kinematic motor performance in 6 subjects following conventional brain MRI (1.5-T). Subjects had a negative neurological examination and fulfilled the diagnostic criteria for RIS proposed by Okuda. Results: Subjects were 4 females and 2 males with a mean age of 39.5 years. 2 subjects performed all kinematic parameters in the range of HC/M, 1 subject resulted with one parameter above the range of HC/M group, 3 subjects had more than 2 kinematic parameters above the range of HC/M. The mean nine-hole peg test (9HPT) score was 18 seconds ± 1. 2 subjects had spinal cervical cord lesions and oligoclonal bands were detected in other 2 patients. VEP were negative in all subjects. No case showed dissemination in time (no new T2 lesions at the 6 month MRI). Of the kinematic parameters used, the integral of the norm of the third derivative-jerk-of the hand path was the most sensitive parameter (four of six subjects), Remarkably the technique appears to be able to detect subtle differences between some subjects with RIS and control subjects. Conclusion: We believe that this type of instrumental assessment can help in identifying subjects with RIS with a high risk for developing MS

Cervical spinal intradural arachnoid cysts in related, young pugs

Seven related young pugs were diagnosed with cervical spinal intradural arachnoid cysts by magnetic resonance imaging (n = 6) and myelography (n = 1). All dogs were presented with skin abrasions on their thoracic limbs and non-painful neurological deficits, indicating a C1-T2 myelopathy. In all six dogs examined by magnetic resonance imaging not only the spinal arachnoid cyst but also a concomitant, most likely secondary, syringohydromyelia was confirmed. Pedigree analysis suggested a genetic predisposition for spinal arachnoid cysts in this family of pugs. Generalised proprioceptive deficits more pronounced in the thoracic limbs suggesting a focal cervical spinal cord lesion, with concomitant skin abrasions on the dorsal aspect of the thoracic limbs in a young pug, should alert veterinarians to the possibility of cervical spinal arachnoid cysts.

Intractable hiccup caused by spinal cord lesions in demyelination disease

ObjectiveThis study aimed to summarize the clinical features of patients who presented intractable hiccup (IH) without brain and medulla oblongata (MO) lesions.MethodThis study included six patients who were diagnosed with inflammatory demyelinating myelitis, categorized as neuromyelitis optica (NMO), multiple sclerosis (MS), and myelitis. Patients who presented IH with cervical lesions but without MO lesions were also included. Clinical profiles, laboratory data, and magnetic resonance imaging findings were analyzed.ResultsThree out of six patients were diagnosed with NMO, whereas the remaining three were diagnosed with acute myelitis, recurrent myelities, and MS, respectively. The duration of hiccup was from 2 to 23 days (average = 9.33 ± 8.64 days). Five patients (83.33%, patients 1–5) had long segmental lesions and one had a patchy lesion. None of these patients had any MO lesions. Half of them were successfully treated with high-dose methylprednisolone combined with gamma-aminobutyric acid (GABA) inhibitor.ConclusionIH occurred in patients without MO lesion. However, the mechanism remained unclear. Immune factors of demyelinating neuropathy stimulated the hiccup reflex arch. Cervical cord lesions may activate the hiccup center. In general, IH can be controlled by IVMP combined with GABA inhibitor. Unilateral phrenic nerve block may elicit no effect.

Relevance of Spinal Cord Abnormalities to Clinical Disability in Multiple Sclerosis: MR Imaging Findings in a Large Cohort of Patients

To determine whether spinal cord atrophy differs among disease subtypes in multiple sclerosis (MS) and whether it offers diagnostic and clinical correlative information beyond that provided by other magnetic resonance (MR) imaging markers. The institutional review board approved the study; all subjects gave written informed consent. Upper cervical cord cross-sectional area (UCCA), brain and spinal cord lesion loads, and brain atrophy were measured in 440 patients with MS (311 with relapsing-remitting [RR] MS, 92 with secondary-progressive [SP] MS, and 37 with primary-progressive [PP] MS) studied in two centers. Disability was scored with the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (TWT), and the nine-hole peg test. UCCA was compared between groups with the Mann-Whitney U test. Correlations were assessed with the Spearman ρ test. Multivariate associations between UCCA and clinical and other MR imaging parameters, including number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord, were assessed by using multiple linear regression, adjusted for study center site. The UCCA in patients with SP MS (median, 79 mm(2); interquartile range, 72.4-84.9 mm(2)) and PP MS (median, 77.3 mm(2); interquartile range, 69-82.5 mm(2)) was significantly smaller (P < .001) than that in patients with RR MS (median, 84 mm(2); interquartile range, 78.7-89.3 mm(2)). UCCA was inversely correlated with EDSS score, TWT, and nine-hole peg test findings (ρ ≤ -0.29, P < .001 for all comparisons). UCCA, number of hypointense brain lesions on T1-weighted MR images, presence of diffuse abnormalities, and number of involved segments in the spinal cord were found to be significant explanatory factors for clinical disability (R(2) = 0.564). The UCCA and the number of hypointense brain lesions on T1-weighted images were the strongest MR imaging parameters for explaining physical disability, as measured with the EDSS. Spinal cord abnormalities have a strong effect on clinical disability in MS. MR imaging-derived UCCA was found to be the most significant spinal cord parameter for explaining EDSS score.

Aquaporin-4 antibodies, CNS acidosis and neuromyelitis optica: A potential link

BackgroundNeuromyelitis optica (NMO, Devic’s syndrome) is a severely disabling disorder of the central nervous system characterized by optic neuritis and longitudinally extensive myelitis. In around 80% of cases, NMO is caused by autoantibodies to astrocytic aquaporin-4 (AQP4), the most abundant water channel in the CNS. Acute NMO attacks are frequently accompanied by elevated levels of lactate in the cerebrospinal fluid (CSF). As a strongly dissociated anion (pK′=3.7) directly changing the strong ion difference, lactate causes a reduction in the dependent anion [HCO3-] and a rise in [H+], resulting in “metabolic” acidosis in the CSF. CSF acidosis also develops during respiratory failure due to brainstem or high cervical spinal cord lesions, the most common cause of death in NMO. However, lactic acid and more generally, a decrease in pH, has been shown to increase the membrane expression of AQP4 in astrocytes. An increase in AQP4 membrane expression during acute NMO attacks could potentially enhance the complement-mediated humoral immune reaction against AQP4-expressing astrocytes characteristic for NMO and, thus, result in more severe astrocytic damage. Moreover, lactate and acidosis have been shown to cause astrocytic swelling and to affect astrocytic viability, potentially rendering astrocytes more susceptible to AQP4-Ab-mediated damage. Finally, increased AQP4 expression could be an independent risk factor in NMO and other forms of CNS inflammation, as indicated by the finding of grossly attenuated experimental autoimmune encephalomyelitis in AQP4-null mice. Therefore, we hypothesize that CSF acidosis might play a role in the pathophysiology of AQP4-Ab-positive NMO and that alterations in CSF pH might possibly influence the outcome of acute attacks in this condition. In addition, we discuss potential clinical implications and make proposals on how to test the hypothesis. Finally, other factors that influence astrocytic AQP4 membrane expression and might play a role in NMO are discussed.

Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis

Lower prevalence of cerebrospinal fluid oligoclonal IgG bands (IgG-OCBs) has been reported in multiple sclerosis (MS) patients from Southern Europe compared to other western countries. ObjectivesWe aimed to determine the prevalence of CSF OCBs in Greek MS patients and to examine their relation with some selected clinical and demographical features. MethodsIncluded patients fulfilled the 2005 McDonald criteria for definite MS (CDMS) or clinically isolated syndrome (CIS) and had a spinal tap performed between 2006 and 2010. Paired CSF and plasma samples were analyzed using isoelectric focusing followed by IgG-specific immunofixation. A pattern of two or more bands present only in the CSF was defined as positive. OCB status was correlated with age at disease onset, initial symptomatology, relapse rate, disease subtype, disease duration, medication, EDSS score and MSSS. ResultsOf the 231 included patients (53.2% with CDMS and 48.6% with CIS) 67.5% had OCBs. The prevalence of positive patterns did not differ between CIS and CDMS patients (67.6% vs. 67.5%, respectively). OCB-positive patients were younger than OCB-negative patients (35.2±10.3 vs. 38.7±11.8 years respectively, p=0.022) and had more frequently cervical spinal cord lesions (x2=7.08, p=0.008). No difference was observed between the two subgroups in the other studied disease parameters. ConclusionDespite the lower frequency of positive IgG-OCB patterns in our patients, both subgroups were mostly similar with regard to their clinical and demographic characteristics suggesting that the OCB status lacks prognostic significance in MS.