ABSTRACT: The "chronic cerebrospinal venous insufficiency" or "CCSVI" hypothesis, namely that multiple sclerosis (MS) is caused by abnormalities in the azygous and internal jugular veins with subsequent alterations in venous hemodynamics in the central nervous system, has been a dominant topic in MS care in Canada over the past year. Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk.
Chart and patient review of five patients with confirmed MS followed in Calgary were undertaken after patients came to medical attention by referral or admission secondary to complications believed to be associated with CCSVI procedures.
Complications upon investigation and review included internal jugular vein stent thrombosis, cerebral sinovenous thrombosis, stent migration, cranial nerve injury and injury associated with venous catheterization.
As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. As increasing numbers of MS patients are seeking such procedures, these five cases represent the beginning of a wave of complications for which standardized care guidelines do not exist. Our experience and that of our colleagues will be used to develop guidelines and strategies to monitor and manage these patients as their numbers increase.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 09/2011; 38(5):741-6. · 0.97 Impact Factor
ABSTRACT: To characterize the effect of vitamin D(3) intake on urinary calcium:creatinine ratios across predefined ranges of serum 25(OH)D.
Patients with multiple sclerosis (n=25) received escalating doses of vitamin D(3) (4000-40,000IU/d) with calcium (1200mg/d).
Urinary calcium:creatinine was driven by increased 25(OH)D when concentrations were <75nmol/L (r=0.424, p=0.009) and >200nmol/L (r=0.281, p=0.01), but no relationship existed when 25(OH)D concentrations were 76-200nmol/L.
A "safe", physiological range of 25(OH)D concentrations is 75-200nmol/L.
Clinical biochemistry 07/2011; 44(10-11):930-2. · 2.02 Impact Factor
ABSTRACT: The active metabolite of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], is a potent modulator of immune cells in vitro.
Our objective was to determine whether the sun-dependent nutrient, cholecalciferol, can alter disease-associated cellular immune abnormalities in patients with multiple sclerosis (MS).
This was an open-label, 12-month, randomized controlled trial.
Patients with MS were recruited from the MS Clinic at St. Michael's Hospital, Toronto.
Forty-nine patients were matched (for age, sex, disease duration, disease-modifying drug, and disability) and enrolled (treated n = 25; control n = 24). Four patients were lost to follow-up (n = 2 from each group).
Treated patients received increasing doses of cholecalciferol (4,000-40,000 IU/d) plus calcium (1200 mg/d), followed by equilibration to a moderate, physiological intake (10,000 IU/d). Control patients did not receive supplements.
At enrollment and at 12 months, peripheral blood mononuclear cell (PBMC) proliferative responses to disease-associated, MS-relevant, and control antigens were measured, along with selected serum biochemical markers.
At 12 months, mean serum 25-hydroxyvitamin D [25(OH)D] concentrations were 83 ± 35 nmol/liter and 179 ± 76 nmol/liter in control and treated participants, respectively (paired t, P < 0.001). Serum 1,25(OH)(2)D did not differ between baseline and 1 yr. In treated patients, 12-month PBMC proliferative responses to neuron antigens myelin basic protein and exon-2 were suppressed (P = 0.002). In controls, there were no significant changes in disease-associated PBMC responsiveness. There were no significant differences between groups in levels of selected biomarkers.
MS-associated, abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH)D concentrations higher than 100 nmol/liter.
The Journal of clinical endocrinology and metabolism 06/2011; 96(9):2826-34. · 6.50 Impact Factor
ABSTRACT: Multiple Sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS), is characterized by recurrent relapses of CNS inflammation ranging from mild to severely disabling. Relapses have long been treated with steroids to reduce inflammation and hasten recovery. However, the commonly used intravenous methylprednisolone requires repeated infusions with the added costs of homecare or hospitalization, and may interfere with daily responsibilities. Oral steroids have been used in place of intravenous steroids, with lower direct and indirect costs.
The primary objective was to compare efficacy of oral versus intravenous steroids for MS relapses <= 6 weeks. Secondary comparisons included subsequent relapse rate, disability, ambulation, hospitalization, immunological markers, radiological markers, and quality of life.
A literature search was performed using Cochrane MS Group Trials Register (July 2008), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2008, issue 3, MEDLINE (PubMed) (1966-July 2008), EMBASE (1980-July 2008), abstracts from meetings of the American Academy of Neurology (2002-2008), the European Federation of Neurological Sciences (2002-2008), the European Committee for Treatment and Research in Multiple Sclerosis and American Committee for Treatment and Research in Multiple Sclerosis (2002-2008) handsearching. No language restrictions were applied.
Randomized or quasi-randomized trials comparing oral and intravenous steroids for acute relapses (<=30 days) in clinically definite MS patients over age 16 were eligible.
Methodological was assessed using trial publications and personal communication. Elevant data was extracted, and effect size was reported as mean difference (MD),weighted mean difference (WMD), odds ratio (OR) and absolute risk difference (ARD).
Eligible studies (167 patients) were identified. Only one outcome, the proportion of patients with EDSS improvement at 4 weeks, was common to three trials. Otherwise outcomes were too heterogeneous to pool. Only one trial employed an equivalence design, but all reported no statistically significant difference in outcomes between groups. Namely, there was no significant difference in the degree of recovery 4 weeks following treatment. No difference was found in subsequent relapse rate, disability, hospitalization, ambulation, bioavailability, or in magnetic resonance imaging (MRI). Due to methodological limitations, heterogeneous treatment regimens and limited data, formal conclusions about equivalence of oral and intravenous steroidscannot be made. Oral Megadose Corticosteroid Therapy of Acute Exacerbations of Multiple Sclerosis (OMEGA) trial, designed to address such limitations, is currently underway.
The trials reviewed support the hypothesis that no significant differences in clinical, radiological or pharmacological outcomes oral and intravenous steroids for MS relapses exist. However, with the small number of patients and methodological limitations, conclusions of equivalence are premature.
Cochrane database of systematic reviews (Online) 01/2009; · 5.72 Impact Factor
Neurology 12/2008; 71(22):1833-4. · 8.31 Impact Factor
ABSTRACT: In 1993, interferon beta-1b, the first clinically proven disease-modifying agent for multiple sclerosis, was approved, with several comparable agents following close behind. These agents have been beneficial in reducing relapse events and MRI lesions, but all require parenteral administration, leading some otherwise eligible patients to decline such therapies. Oral agents have been studied for decades with mixed results, but a small number of medications currently being tested in phase II/III clinical trials have shown promise in efficacy and tolerability. This review assesses the results of the more thoroughly studied of these agents, some of which may soon be approved for use in multiple sclerosis.
Current Neurology and Neuroscience Reports 06/2007; 7(3):223-30. · 3.45 Impact Factor
ABSTRACT: Over the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada.
Patients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented.
In August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised.
The most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 06/2004; 31(2):185-93. · 0.97 Impact Factor