Lamb, Christopher J

Background and Purpose: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings. Methods: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records. Results: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke. Conclusion: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.

Abstract Delayed diagnosis of immune-mediated necrotizing myopathy leads to increased morbidity. Patients with the chronic course without 3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG or signal recognition particle-IgG are often challenging to diagnose. Immunotherapy response can also be difficult to assess. We created a statistical model to assist immune-mediated necrotizing myopathy diagnosis. Electrical myotonia versus fibrillations were reviewed as biomarkers for immunotherapy treatment response. Identified were 119 immune-mediated necrotizing myopathy cases and 938 other myopathy patients. Inclusion criteria included all having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and 67% (20/30) of our validation immune-mediated necrotizing myopathy cohorts, and significantly (P < 0.001) favoured immune-mediated necrotizing myopathy over other myopathies: sporadic inclusion body myositis (odds ratio = 4.78); dermatomyositis (odds ratio = 10.61); non-specific inflammatory myopathies (odds ratio = 8.46); limb-girdle muscular dystrophies (odds ratio = 5.34) or mitochondrial myopathies (odds ratio = 14.17). Electrical myotonia occurred in immune-mediated necrotizing myopathy seropositive (3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG 70%, 37/53; signal recognition particle-IgG 29%, 5/17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in combination accurately predicted immune-mediated necrotizing myopathy (97.1% area-under-curve). The model was validated in a separate cohort of 30 immune-mediated necrotizing myopathy cases. Delayed diagnosis of cases with electrical myotonia occurred in 24% (16/67, mean 8 months; range 0–194). Half (8/19) had a chronic course and were seronegative, with high model prediction (>86%) at the first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2–124) which reduced from 36% (58/162) of muscles to 7% (8/121; P < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as with median creatine kinase reduction of 1779 U/l (range 401–9238, P < 0.001). Modelling clinical features with electrical myotonia is especially helpful in immune-mediated necrotizing myopathy diagnostic suspicion among chronic indolent and seronegative cases. Electrical myotonia favours immune-mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy biomarker.

AbstractIntroductionThe sensitivity of repetitive nerve stimulation (RNS) in myasthenia gravis (MG) is dependent on the cutoff for abnormal decrement.MethodsRNS data of adults with and without MG from 2014 to 2017 were reviewed retrospectively. The maximum reliable RNS amplitude/area decrement before and after exercise from facial, spinal accessory (SA), ulnar, and fibular nerves was recorded. Sensitivity/specificity using 5%, 7%, and 10% cutoffs were calculated.ResultsSeventy‐nine of 141 patients had MG (46 generalized, 21 ocular, 12 bulbar). A total of 608 unique RNS recordings were analyzed. Overall RNS sensitivity/specificity at ≥5%, ≥7%, and ≥10% amplitude cutoffs were as follows: SA, 65.6%/86.3%, 49.2%/94.1%, and 29.5%/96.1%; facial, 51.0%/82.5%, 43.1%/95.0%, and 37.3%/100%; ulnar, 43.6%/100%, 41.0%/100%, and 41.0%/100%; and fibular, 52.6%/89.5%, 42.1%/94.7%, and 42.1%/100%.DiscussionLowering amplitude cutoff from 10% to 7% increased or maintained sensitivity with little loss in specificity. Post‐exercise and area analysis resulted in increased sensitivity in some circumstances.

SummaryObjectiveTo characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine‐rich glioma inactivated‐1 ( LGI1‐Ab) autoimmune epilepsy (AE).MethodsPatients with voltage‐gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1‐Ab positive and were treated for seizures.ResultsA total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic–clonic (GTCs) (n = 28, 50%), and focal non‐motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty‐eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non‐NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001).SignificanceAlthough FBDS are the most characteristic seizure type seen in LGI1‐Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1‐Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB‐blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.

ABSTRACTIntroductionVoluntary doublets are electrophysiological phenomena thought to be associated with metabolic derangements or neuromuscular conditions.MethodsWe prospectively studied 232 consecutive patients examined by a single examiner during routine electromyography (EMG) to determine the frequency of doublets in individual patients, specific muscles, neuromuscular conditions, electrolyte levels, and doublet characteristics.ResultsOf 232 patients, 25 (10.7%) exhibited doublets. The mean age was 59 (52% men). Only 32 of 1,303 (2.5%) muscles exhibited doublets. Lower extremity and paraspinal groups represented 91% of muscles with doublets. Doublet frequency grouped by EMG diagnoses was: ALS (3 of 11; 27.1%), myopathy (3 of 10; 30.0%), axonal polyneuropathy (7 of 29; 24.1%), and no disease (7 of 109; 6.4%). There were no differences in serum electrolytes between doublet and matched subjects.ConclusionsDoublets occur in approximately 10% of patients, more commonly in lower extremity and paraspinal muscles, and are not correlated with a specific metabolic abnormality or neuromuscular condition. Muscle Nerve 55: 598–600, 2017