Lempert, Thomas

ABSTRACT Aims Sarcoid myopathy (SaM) is characterised by granulomatous myositis (GM) and can overlap with inclusion body myositis (IBM), a late‐onset chronic idiopathic inflammatory myopathy with a still enigmatic pathogenesis. As GM can occur in different clinical contexts, we aimed to examine the histomorphologic features and gene expression profiles in cases of definite SaM that may inform diagnostic and therapeutic considerations. Methods We performed a multidimensional characterisation of muscle biopsy specimens from patients with ‘pure SaM’ (n=17), SaM with concomitant IBM (SaM‐IBM) (n=2), including histopathologic and ultrastructural analysis in addition to quantitative real‐time polymerase chain reaction. Additionally, bulk RNA sequencing was performed on 38 muscle biopsy specimens from patients with SaM (including SaM‐IBM) (n=30) and NGI (n=8). Results Histopathological analysis revealed a pattern of endomysial and perimysial granulomatous inflammation frequently extending to the fascia, endomysial fibrosis, muscle fibre atrophy, variation in muscle fibre size and capillary thickening. Findings from immunohistochemical studies established Chitinase 1 as a pure giant cell marker in SaM. On a subcellular level, ‘pure SaM’ was characterised by focal accumulation of large swollen mitochondria with rare cristae but an absence of irregular cristae. Transcriptomic analysis of patients with SaM confirmed markedly elevated expression of both type 1 and type 2 human leukocyte antigen molecules. Macrophage activity markers were highly elevated. Consistent with histologic findings, CHIT1 was specifically overexpressed in SaM samples but not in ‘pure IBM’ muscle biopsy specimens. Conclusions SaM is characterised by a stereotypical appearance at the histopathologic level and disease‐specific immune dysregulation that involves macrophage function and maturation. SaM‐IBM represents a noteworthy overlap syndrome that shares multiple dysregulated immune pathways with ‘pure SaM’.

In 2007, the Bárány Society embarked on a project to establish definitions of vestibular syndromes and disorders based on best available evidence, referred to as the International Classification of Vestibular Disorders (ICVD). Since then, numerous publications providing consensus-driven diagnostic criteria for vestibular symptoms, syndromes, and disorders have been published. Here, we reflect on the rationale for developing the ICVD as well as its subsequent achievements, challenges, and outlook. In this summary of the work of the ICVD to date, the authors will focus on practical aspects to help improve the utility and applicability of these diagnostic criteria moving forward.

This paper describes the diagnostic criteria for “Vestibular Migraine of Childhood”, “probable Vestibular Migraine of Childhood” and “Recurrent Vertigo of Childhood” as put forth by the Committee for the Classification of Vestibular Disorders of the Bárány Society (ICVD) and the Migraine Classification subgroup of the International Headache Society. Migraine plays an important role in some subgroups of children with recurrent vertigo. In this classification paper a spectrum of three disorders is described in which the migraine component varies from definite to possibly absent. These three disorders are: Vestibular Migraine of Childhood, probable Vestibular Migraine of Childhood and Recurrent Vertigo of Childhood. The criteria for Vestibular Migraine of Childhood (VMC) include (A) at least five episodes with vestibular symptoms of moderate or severe intensity, lasting between five minutes and 72 hours, (B) a current or past history of migraine with or without aura, and (C) at least half of episodes are associated with at least one migraine feature. Probable Vestibular Migraine of Childhood (probable VMC) is considered when at least three episodes with vestibular symptoms of moderate or severe intensity, lasting between five minutes and 72 hours, are accompanied by at least criterion B or C from the VMC criteria. Recurrent Vertigo of Childhood (RVC) is diagnosed in case of at least three episodes with vestibular symptoms of moderate or severe intensity, lasting between 1 minute and 72 hours, and none of the criteria B and C for VMC are applicable. For all disorders, the age of the individual needs to be below 18 years old. It is recommended that future research should particularly focus on RVC, in order to investigate and identify possible subtypes and its links or its absence thereof with migraine.

This paper presents the diagnostic criteria for hemodynamic orthostatic dizziness/vertigo to be included in the International Classification of Vestibular Disorders (ICVD). The aim of defining diagnostic criteria of hemodynamic orthostatic dizziness/vertigo is to help clinicians to understand the terminology related to orthostatic dizziness/vertigo and to distinguish orthostatic dizziness/vertigo due to global brain hypoperfusion from that caused by other etiologies. Diagnosis of hemodynamic orthostatic dizziness/vertigo requires: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) orthostatic hypotension, postural tachycardia syndrome or syncope documented on standing or during head-up tilt test; and C) not better accounted for by another disease or disorder. Probable hemodynamic orthostatic dizziness/vertigo is defined as follows: A) five or more episodes of dizziness, unsteadiness or vertigo triggered by arising or present during upright position, which subsides by sitting or lying down; B) at least one of the following accompanying symptoms: generalized weakness/tiredness, difficulty in thinking/concentrating, blurred vision, and tachycardia/palpitations; and C) not better accounted for by another disease or disorder. These diagnostic criteria have been derived by expert consensus from an extensive review of 90 years of research on hemodynamic orthostatic dizziness/vertigo, postural hypotension or tachycardia, and autonomic dizziness. Measurements of orthostatic blood pressure and heart rate are important for the screening and documentation of orthostatic hypotension or postural tachycardia syndrome to establish the diagnosis of hemodynamic orthostatic dizziness/vertigo.