Epstein-Barr virus associated CNS lymphoproliferative disorder after long-term immunosuppression.

The incidence of Epstein-Barr virus (EBV)associated lymphoproliferative disorders has increased with greater use of immunomodulatory therapies. We present a woman who developed subacute cognitive decline and unilateral weakness while taking long-term mycophenolate mofetil for granulomatosis with polyangiitis; her postmortem brain histopathology confirmed an EBV-driven lymphoproliferative disorder. Clinicians must have a high index of suspicion for EBV-driven lymphoma in people taking long-term immunosuppression who develop new neurological problems. We review the role of mycophenolate mofetil in EBV-driven lymphoproliferative disorders, and discuss checking EBV status in all patients starting immunosuppression and in older people already taking immunosuppression.

Long QT syndrome masquerading as epilepsy.

The diagnosis of epilepsy is incorrect in up to 20% of cases so should be revisited if attacks are not responding to treatment. We present a case of long QT syndrome that remained undiagnosed in the epilepsy clinic for 15 years until a near-fatal arrhythmia revealed the diagnosis and allowed effective treatment of her attacks. We hope this near miss raises awareness of long QT syndrome as a potentially fatal, rare but treatable condition that neurologists must consider in people with a label of refractory epilepsy. We provide practical pointers to increase the chance of early diagnosis and explore the impact of a late diagnosis for the patient and her family.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

BACKGROUND AND OBJECTIVES: Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. METHODS: The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. RESULTS: Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. DISCUSSION: ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes.

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.

A new mitochondrial transfer RNAPro gene mutation associated with myoclonic epilepsy with ragged-red fibers and other neurological features.

BACKGROUND: Pathogenic mutations of the human mitochondrial genome are associated with well-characterized, progressive neurological syndromes, with mutations in the transfer RNA genes being particularly prominent. OBJECTIVE: To describe a novel mitochondrial transfer RNA(Pro) gene mutation in a woman with a myoclonic epilepsy with ragged-red fibers-like disease. Design, Setting, and Patient Case report of a 49-year-old woman presenting with a myoclonic epilepsy with ragged-red fibers-like disease comprising myoclonic jerks, cerebellar ataxia, and proximal muscle weakness. RESULTS: Histochemical analysis of a muscle biopsy revealed numerous cytochrome-c oxidase-deficient, ragged-red fibers, while biochemical studies indicated decreased activity of respiratory chain complex I. Molecular investigation of mitochondrial DNA revealed a new heteroplasmic mutation in the TpsiC stem of the mitochondrial transfer RNA(Pro) gene that segregated with cytochrome-c oxidase deficiency in single muscle fibers. CONCLUSIONS: Our case serves to illustrate the ever-evolving phenotypic spectrum of mitochondrial DNA disease and the importance of performing comprehensive mitochondrial genetic studies in the absence of common mitochondrial DNA mutations.