Diagnosis and Treatment of Multiple Sclerosis: A Review McGinley, Marisa P; Goldschmidt, Carolyn H; Rae-Grant, Alexander D
JAMA : the journal of the American Medical Association,
02/2021, Letnik:
325, Številka:
8
Journal Article
Recenzirano
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.
ABSTRACT
Introduction: Antibody against the acetylcholine receptor of autonomic ganglia (gAChR‐Ab) is implicated in the pathogenesis of autoimmune autonomic ganglionopathy (AAG) and several other ...disorders. Methods: This study was a retrospective evaluation of 95 patients positive for gAChR‐Ab. Results: Twenty‐one (22%) patients had AAG, with a greater median gAChR‐Ab level (0.21 nmol/L) and higher percentage (57%) of antibody levels >0.20 nmol/L when compared with the remaining 74 patients without autonomic manifestations (non‐AAG group, 0.10 nmol/L and 15%, respectively). Only 2 new cases of malignancy were diagnosed after gAChR‐Ab detection. The non‐AAG group was associated with high frequencies of neurological and non‐neurological autoimmunity, but also included 23 (31%) patients with mostly degenerative disorders. Conclusion: Detection of gAChR‐Ab, especially at a higher level, is helpful for the diagnosis of AAG in patients with corresponding autonomic symptoms. However, its value is limited for predicting cancer risk and for diagnosis and management of patients without autonomic symptoms. Muscle Nerve 52:386–391, 2015
•Rhythmic delta is increasingly seen in anti-NMDA receptor encephalitis (NMDARE) refractory to first line immunotherapy.•Rhythmic delta decreases after second line immunotherapy and predates clinical ...improvement.•Rhythmic delta is not seen in other autoimmune encephalitides and is likely specific to NMDARE.
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.
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.
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.
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.
Extreme delta may be a surrogate marker of disease activity in NMDARE refractory to first line immunotherapy.
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.
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.
Persistent apnea despite an adequate rise in arterial pressure of CO
is an essential component of the criteria for brain death (BD) determination. Current guidelines vary regarding the utility of ...arterial pH changes during the apnea test (AT). We aimed to study the effect of incorporating an arterial pH target < 7.30 during the AT (in addition to the existing PaCO
threshold) on brain death declarations.
We performed retrospective analysis of consecutive adult patients who were diagnosed with BD and underwent AT at the Cleveland Clinic over the last 10 years. Data regarding baseline and post-AT blood gas analyses were collected and analyzed.
Ninety-eight patients underwent AT in the study period, which was positive in 89 (91%) and inconclusive in 9 (9%) patients. The mean age was 50 years old (standard deviation SD 16) and 54 (55%) were female. The most common etiology BD was hypoxic ischemic brain injury (HIBI) due to cardiac arrest (42%). Compared to those with positive AT, patients with inconclusive AT had a higher post-AT pH (7.24 vs 7.17, p = 0.01), lower PaO
(47 vs 145, p < 0.01), and a lower PaCO
(55 vs 73, p = 0.01). Among patients with a positive AT using PaCO
threshold alone, the frequency of patients with post-AT pH < 7.30 was 95% (83/87).
Implementing a BD criteria requiring both arterial pH and PaCO
thresholds reduced the total number of positive ATs; these inconclusive cases would have required longer duration of AT to reach both targets, repeated ATs, or ancillary studies to confirm BD. The impact of this on the overall number BD declarations requires further research.
Now in its third edition, Ultimate Review for the Neurology Boards is the definitive study guide for anyone preparing for the neurology board exam, RITE, or MOC exam. Compiled by nearly two dozen ...contributors and edited by four leading neurologists from the Cleveland Clinic, this comprehensive point form review presents thelatest research, data, and knowledge on all aspects of neurology that you need to know to succeed on these exams.
The book is organized into five sections for easy access and concludes with a practice test. The first section covers basic neurosciences, including neurochemistry, clinical neuroanatomy, andgenetics. The next section discusses clinical neurology, with chapters devoted to the major diseases and disorders including stroke, head trauma, dementia,epilepsy, and movement disorders, among others. In the third section, NCS, EMG, EEG, evoked potentials, and sleep neurology are covered, with images to enhance understanding of fundamental neurophysiologic techniques. After a dedicated chapter on pediatric neurology, the final section contains nine chapters on subspecialties, including neurorehabilitation, adult and child psychiatry, neurourology, neuro-oncology, and more.
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.
To describe apnoea test (AT) and ancillary study performance for brain death (BD) determination among patients undergoing short-term mechanical circulatory support (MCS) devices, including ...extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP).
We retrospectively analysed data regarding use of AT and ancillary study in consecutive adult patients who were diagnosed with BD while on MCS devices (including ECMO and IABP) over a 10-year period.
Out of 140 patients, eight were on MCS devices at the time of BD (four ECMO, two ECMO and IABP, two IABP). The most common aetiology of BD was hypoxic ischaemic brain injury (6/8, 75%). In four patients (50%), the AT was not attempted because of haemodynamic instability and ECMO; in the remaining four (50%), both AT and ancillary studies were used. In three patients on ECMO, AT was performed by reducing the ECMO sweep flow rate to a range 0.5–2.7 L/min in order to achieve hypercarbia. One patient underwent AT while on IABP which was complicated by hypotension. All patients underwent ancillary tests, most commonly transcranial Doppler ultrasonography (TCD) (7/8, 88%); among those, cerebral circulatory arrest was confirmed in six of seven patients (86%), all of whom had left ventricular ejection fracture (LVEF) ≥20% and/or were supported with IABP.
There are multiple uncertainties regarding BD diagnosis while on MCS, prompting the need for ancillary studies in most patients. Our study shows that TCD can be used to support BD diagnosis in patients on ECMO who have sufficient cardiac contractility and/or IABP to produce pulsatile flow. TCD use in ECMO patients low LVEF needs further study.
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