Peripheral nervous system manifestations of MOG antibody associated disease.

Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG-IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true-positive MOG-IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

Acute symptomatic seizures secondary to myelin oligodendrocyte glycoprotein antibody-associated disease.

OBJECTIVE: To report the clinical presentations and outcomes of patients with seizure and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). METHODS: We retrospectively reviewed the electronic medical records for clinical and paraclinical features among patients with seizures and MOG-IgG (immunoglobulin G) seropositivity. RESULTS: We identified 213 patients with MOG-IgG seropositivity who fulfilled criteria for MOGAD. Seizures attributed to central nervous system (CNS) autoimmunity were observed in 10% of patients (n = 23: 19 children, 4 adults). The majority (n = 19, 83%) had pediatric disease onset. Focal motor seizures were the most common seizure semiology (16/23; 70%). Focal to bilateral tonic-clonic seizures were present in 12 patients (53%), and 3 patients (13%) developed status epilepticus. All patients had features of encephalitis at onset of seizures. Cerebral cortical encephalitis (CCE) was the most common radiological finding (10 unilateral and 5 bilateral cases). Eight of 23 patients (35%) had only CCE, six of 23 patients (26%) had only acute disseminated encephalomyelitis (ADEM), and seven of 23 patients (30%) had features of both. Fifteen patients (65%) had leptomeningeal enhancement. Three patients (13%) had coexistence of N-methyl-d-aspartate receptor (NMDAR) IgG. Only 3 of 23 patients (13%) developed drug- resistant epilepsy. Although the majority had MOGAD relapses (14/23, 60%) had only 5 of 23 patients had recurrence of episodes of encephalitis with associated seizures. Twenty-one of 23 patients (91%) had seizure freedom at last follow-up. SIGNIFICANCE: MOG-IgG evaluation should be considered in patients who present with encephalitis and focal motor and/or focal to bilateral tonic-clonic seizures, especially pediatric patients with magnetic resonance imaging (MRI) brain findings consistent with CCE, ADEM, or other MOGAD presentations. The majority of these seizures are self-limited and do not require maintenance/chronic antiseizure medications. Although seizure recurrence is uncommon, many patients have MOGAD relapses in the form of encephalitis and optic neuritis.

Identification of Caveolae-Associated Protein 4 Autoantibodies as a Biomarker of Immune-Mediated Rippling Muscle Disease in Adults.

Importance: Immune-mediated rippling muscle disease (iRMD) is a rare myopathy characterized by wavelike muscle contractions (rippling) and percussion- or stretch-induced muscle mounding. A serological biomarker of this disease is lacking. Objective: To describe a novel autoantibody biomarker of iRMD and report associated clinicopathological characteristics. Design, Setting, and Participants: This retrospective cohort study evaluated archived sera from 10 adult patients at tertiary care centers at the Mayo Clinic, Rochester, Minnesota, and Brigham & Women's Hospital, Boston, Massachusetts, who were diagnosed with iRMD by neuromuscular specialists in 2000 and 2021, based on the presence of electrically silent percussion- or stretch-induced muscle rippling and percussion-induced rapid muscle contraction with or without muscle mounding and an autoimmune basis. Sera were evaluated for a common biomarker using phage immunoprecipitation sequencing. Myopathology consistent with iRMD was documented in most patients. The median (range) follow-up was 18 (1-30) months. Exposures: Diagnosis of iRMD. Main Outcomes and Measures: Detection of a common autoantibody in serum of patients sharing similar clinical and myopathological features. Results: Seven male individuals and 3 female individuals with iRMD were identified (median [range] age at onset, 60 [18-76] years). An IgG autoantibody specific for caveolae-associated protein 4 (cavin-4) was identified in serum of patients with iRMD using human proteome phage immunoprecipitation sequencing. Immunoassays using recombinant cavin-4 confirmed cavin-4 IgG seropositivity in 8 of 10 patients with iRMD. Results for healthy and disease-control individuals (n = 241, including myasthenia gravis and immune-mediated myopathies) were cavin-4 IgG seronegative. Six of the 8 individuals with cavin-4 IgG were male, and the median (range) age was 60 (18-76) years. Initial symptoms included rippling of lower limb muscles in 5 of 8 individuals or all limb muscles in 2 of 8 sparing bulbar muscles, fatigue in 9 of 10, mild proximal weakness in 3 of 8, and isolated myalgia in 1 of 8, followed by development of diffuse rippling. All patients had percussion-induced muscle rippling and half had percussion- or stretch-induced muscle mounding. Four of the 10 patients had proximal weakness. Plasma creatine kinase was elevated in all but 1 patient. Six of the 10 patients underwent malignancy screening; cancer was detected prospectively in only 1. Muscle biopsy was performed in 7 of the 8 patients with cavin-4 IgG; 6 of 6 specimens analyzed immunohistochemically revealed a mosaic pattern of sarcolemmal cavin-4 immunoreactivity. Three of 6 patients whose results were seropositive and who received immunotherapy had complete resolution of symptoms, 1 had mild improvement, and 2 had no change. Conclusions and Relevance: The findings indicate that cavin-4 IgG may be the first specific serological autoantibody biomarker identified in iRMD. Depletion of cavin-4 expression in muscle biopsies of patients with iRMD suggests the potential role of this autoantigen in disease pathogenesis.

Erenumab for episodic migraine.

In this review, the authors provide an overview of erenumab, a monoclonal antibody used for the preventative treatment of episodic migraine by targeting the CGRP pathway. Randomized controlled trials have shown that erenumab is associated with a statistically significant decrease in monthly migraine days in patients with episodic migraine at monthly doses of 70 or 140 mg when given for a period of 9-12 weeks. Post hoc analyses have also shown long-term maintenance of efficacy. Clinical trials have found erenumab at doses of both 70 and 140 mg to have a favorable safety profile. Erenumab faces significant limitations because of its high financial cost. Additional long-term real-world data are needed to understand the role of erenumab in the treatment of migraine.

In this review, the authors give an overview of erenumab, an injectable medication used to prevent migraine headaches. Erenumab has been proven to be significantly effective in patients with episodic migraines when used at doses of 70 or 140 mg. Furthermore, studies have shown sustained benefit starting as early as the first week of treatment as well as improvement in patients' quality of life. Erenumab has been found to be as safe as placebo in some studies, but there have been some reports of a link to high blood pressure and constipation. However, because of its high cost, patients still face significant barriers to access to erenumab. Additional long-term real-world data are needed to understand the current role of erenumab in the treatment of migraine.

A Review of Eptinezumab Use in Migraine.

We present a review of the efficacy and safety profile of eptinezumab (also known by the brand name Vyepti), a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) developed by Lundbeck Seattle BioPharmaceuticals, Inc., that received its first approval in the USA on 21 February 2020 for the preventive treatment of migraine in adults. It is administered by an intravenous infusion at a 100 mg dose every 3 months and shows no drug interactions. Studies have shown that eptinezumab is an effective preventative medication in migraine which starts showing its effect from day 1 of its administration, which maintains a consistent level of efficacy through a year of its treatment at doses 100 mg and 300 mg. It was found to be effective at reducing time to headache pain freedom during acute migraine attacks as well. Eptinezumab is a relatively safe drug for the prevention of migraines with treatment-related adverse events occurring at a low frequency. They bear a safe profile in patients with comorbidities like obesity and type 1 diabetes. The most frequent adverse events observed were nasopharyngitis, upper respiratory tract infections (URTIs), and sinusitis and were usually mild. The development of anti-drug antibodies was common, but they declined to undetectable levels with continued dosing and did not appear to impact the overall safety profile of the drug. Further studies are needed to assess long-term safety, use in different patient populations, and to compare its efficacy to other drugs of its class.

A Case of Euthyroid Steroid-Responsive Encephalopathy With Subacute Dementia.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), frequently termed as Hashimoto's encephalopathy (HE), is characterized by reversible encephalopathy with the presence of elevated antithyroid antibodies. The condition was initially described due to its association with Hashimoto's thyroiditis. We report a case of euthyroid HE presenting as subacute dementia. A 50-year-old woman presented with progressive memory decline for six weeks. Thyroid function tests, thyroid ultrasound, and cerebrospinal fluid analysis were unremarkable. Electroencephalogram showed generalized slowing with triphasic waves. On magnetic resonance imaging, T1 weighted images revealed hyperintensity in bilateral basal ganglia. Antithyroglobulin and antithyroid peroxidase were markedly elevated. She improved remarkably on tablet prednisolone 60 mg once daily, confirming the suspicion of steroid-responsive encephalopathy. Thus, we conclude that patients with subacute cognitive decline could be screened for antithyroid antibodies in the dementia workup despite their euthyroid status.

Primary Writing Tremor: Current Concepts.

Primary Writing Tremor (PWT) is a type of task specific tremor which happens only while writing (Type A PWT) or assuming a writing position of the hand (Type B PWT). There is a considerable overlap of clinical features between PWT and writer's cramp which creates difficulty in diagnosing this condition in the clinic. PWT usually affects the dominant hand and is typically 5-7hz in frequency, worsened by anxiety, temporarily relieved by alcohol and associated with reduced writing speeds. There are a variety of hypotheses about the phenomenology of PWT (regarding whether it is a variant of essential tremor, focal dystonia or an independent entity). Unlike writer's cramp, PWT shows normal reciprocal inhibition of H reflex, does not exhibit excessive EMG activity in proximal muscles, and on fMRI shows underactivation of cingulum and overactivation of primary motor and supplementary areas. There are no randomised controlled trials currently for the treatment of PWT. Treatment modalities available are: medical treatment, botulinum toxin, surgical management (including DBS) as well as adaptive strategies and occupational therapy.