Publications by authors named "Alexander D Rae-Grant"

6 Publications

  • Page 1 of 1

Diagnosis and Treatment of Multiple Sclerosis: A Review.

JAMA 2021 02;325(8):765-779

Cleveland Clinic Mellen Center, Cleveland, Ohio.

Importance: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS.

Observations: MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid-specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease.

Conclusions And Relevance: MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.
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February 2021

Incorporating Clinical Practice Guidelines and Quality Measures Into High-Quality Cost-Effective Care for Patients With Multiple Sclerosis.

Continuum (Minneap Minn) 2019 06;25(3):845-849

This article presents a hypothetical case of a patient with multiple sclerosis (MS), reviewing the use of clinical practice guidelines and incorporation of quality measures into practice. Appropriate diagnosis of MS is important to avoid the cost and consequences of a misdiagnosis. Ensuring that treatment discussion occurs when a patient with MS is receptive is good clinical practice and a guideline recommendation from the American Academy of Neurology. Continuing dialogue about disease-modifying therapy and ongoing monitoring are important for patient care and improved outcomes. Ultimately, cost-effective care in MS relates to using appropriate medicines in patients with active MS, ensuring adherence, and careful monitoring.
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June 2019

Extreme delta - With or without brushes: A potential surrogate marker of disease activity in anti-NMDA-receptor encephalitis.

Clin Neurophysiol 2018 10 10;129(10):2197-2204. Epub 2018 Mar 10.

Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic Foundation, 1950 E 89th St, Cleveland, OH 44195, USA.

Objective: Anti-NMDA receptor encephalitis (NMDARE) may not respond to first line immunotherapy. Biomarkers to track disease course and guide escalation of immunotherapy are needed. We describe the evolution of EEG in four patients with NMDARE requiring prolonged intensive care.

Methods: Within a database of 121 patients with immune-mediated neurological disorders, ten with NMDARE were retrospectively identified. Four patients did not respond to first line immunotherapy. Continuous EEG was reviewed and correlated with clinical status and treatment.

Results: Intermittent polymorphic delta slowing was present in all patients. Generalized rhythmic delta occupied increasing proportion of the EEG as disease progressed, at times with superimposed beta. The institution of second line immunotherapy was followed by progressive decrease in rhythmic delta, predating clinical improvement. In one patient who did not respond to second line immunotherapy, rhythmic delta continued to occupy a majority of the recording. The extreme delta pattern was not seen in a comparison cohort of patients with autoimmune encephalitis without anti-NMDA-R antibodies.

Conclusions: Extreme delta, with or without brushes, increases with progression of NMDARE, responds to escalation of immunotherapy, predating clinical improvement, and is likely specific to NMDA-R antibodies.

Significance: Extreme delta may be a surrogate marker of disease activity in NMDARE refractory to first line immunotherapy.
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October 2018

Transient neurologic syndromes: A diagnostic approach.

Cleve Clin J Med 2018 Feb;85(2):155-163

Mellen Center for Multiple Sclerosis, Department of Neurology, Cleveland Clinic, Cleveland, OH, USA.

Clinicians are often confronted with patients who have transient neurologic symptoms lasting seconds to hours. In many of these patients, their symptoms have gone away or returned to baseline by the time of evaluation, making the diagnosis even more challenging. Elements such as correlation of symptoms with vascular territory, prodromes, triggers, motor symptoms, confusion, and sleep behavior can guide the diagnostic workup.
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February 2018

Unusual symptoms and syndromes in multiple sclerosis.

Continuum (Minneap Minn) 2013 Aug;19(4 Multiple Sclerosis):992-1006

Mellen Center for Multiple Sclerosis, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.

Purpose Of Review: In multiple sclerosis (MS), symptoms vary widely from patient to patient. Certain events in MS are well recognized (eg, optic neuritis, brainstem and spinal cord relapses) and do not lead to much clinical confusion. However, other events that occur in MS may be less expected and may be underrecognized by some clinicians and may lead to an extensive and potentially unnecessary investigation for what is a known problem in MS.

Recent Findings: This article reviews Lhermitte sign, Pulfrich phenomenon, Uhthoff phenomenon, and the useless hand of Oppenheim, along with the underrecognized phenomena of transient neurologic events (including tonic spasms). Disorders of temperature regulation in MS (likely based on hypothalamic involvement) which can present with bizarre behavioral change and evade diagnosis, are also discussed. The article concludes with a review of epilepsy and sleep disorders in MS, both of which appear to occur at an increased frequency in the MS population and may have implications for therapy.

Summary: This article is meant to help clinicians recognize and treat this fascinating set of underrecognized phenomena in MS and perhaps save patients trips to the emergency department, extraneous testing, and ineffective intervention.
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August 2013

Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy.

Mult Scler 2010 Nov 29;16(11):1335-40. Epub 2010 Jul 29.

Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, USA.

Background: Multiple sclerosis (MS) is usually considered a 'young persons' disease', typically presenting between the ages of 20 and 40. In this study we review our experience with patients diagnosed at age 60 or over, with particular emphasis on patients who continue to have evidence of active inflammation despite a later onset.

Methods: We reviewed all cases of MS diagnosed at or over age 60 in our center over a 5-year period. We identified 111 patients and recorded their clinical and imaging characteristics using prespecified variables. Analyses were performed to describe their interval to diagnosis, clinical syndromes, imaging and laboratory characteristics.

Results: At the time of diagnosis, 8% of patients had a clinically isolated syndrome, 33% were in the relapsing-remitting stage, while 23% had a secondary progressive course, and 32% were primary progressive. Eighty-eight percent of patients had a brain MRI judged 'typical for MS', and 32% of all patients receiving gadolinium had enhanced lesions. Forty-six percent of patients with relapsing-remitting MS or clinically isolated syndrome exhibited gadolinium enhancement. Myelitis was the most common initial clinical syndrome, and progressive myelopathy was a common but not exclusive clinical syndrome at the time of diagnosis.

Conclusions: A relapsing pattern of MS is not uncommon, even in patients diagnosed over the age of 60. Active inflammation (clinical relapses and gadolinium enhancement) occurs in a significant number of patients with MS with later diagnosis. These observations have implications for evaluation and treatment of patients with MS presenting at an older age.
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November 2010