Clinical manifestations of the anti-IgLON5 disease.

OBJECTIVE: To report the presentation, main syndromes, human leukocyte antigen (HLA) association, and immunoglobulin G (IgG) subclass in the anti-IgLON5 disease: a disorder with parasomnias, sleep apnea, and IgLON5 antibodies. METHODS: This was a retrospective clinical analysis of 22 patients. The IgG subclass was determined using reported techniques. RESULTS: Patients' median age was 64 years (range 46-83). Symptoms that led to initial consultation included sleep problems (8 patients; 36%), gait abnormalities (8; 36%), bulbar dysfunction (3; 14%), chorea (2; 9%), and cognitive decline (1; 5%). By the time of diagnosis of the disorder, 4 syndromes were identified: (1) a sleep disorder with parasomnia and sleep breathing difficulty in 8 (36%) patients; (2) a bulbar syndrome including dysphagia, sialorrhea, stridor, or acute respiratory insufficiency in 6 (27%); (3) a syndrome resembling progressive supranuclear palsy (PSP-like) in 5 (23%); and (4) cognitive decline with or without chorea in 3 (14%). All patients eventually developed parasomnia, sleep apnea, insomnia, or excessive daytime sleepiness. HLA-DRB1*10:01 and HLA-DQB1*05:01 were positive in 13/15 (87%) patients; the DRB1*10:01 allele was 36 times more prevalent than in the general population. Among 16 patients with paired serum and CSF samples, 14 had IgLON5 antibodies in both, and 2 only in serum (both had a PSP-like syndrome). Twenty of 21 patients had IgG1 and IgG4 antibodies; the latter predominated in 16. CONCLUSIONS: Patients with IgLON5 antibodies develop a characteristic sleep disorder preceded or accompanied by bulbar symptoms, gait abnormalities, oculomotor problems, and, less frequently, cognitive decline. IgG4 subclass antibodies predominate over IgG1; we confirm a strong association with the HLA-DRB1*10:01 allele.

Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson's disease.

BACKGROUND: Verbal fluency relies on the coordinated activity between left frontal and temporal areas. Patients with Parkinson's disease (PD) present phonemic and semantic fluency deficits. Recent studies suggest that transcranial direct current stimulation (tDCS) enhances adaptative patterns of brain activity between functionally connected areas. OBJECTIVE: The aim of this study was to assess the differences in the effects induced by tDCS applied to frontal and temporo-parietal areas on phonemic and semantic fluency functional networks in patients with PD. METHOD: Sixteen patients were randomized to receive tDCS to left dorsolateral prefrontal cortex (DLPFC) and left temporo-parietal cortex (TPC) in a counterbalanced order. Immediately following stimulation, patients underwent a verbal fluency paradigm inside a fMRI scanner. Changes induced by tDCS in activation and deactivation task-related pattern networks were studied using free-model independent component analyses (ICA). RESULTS: Functional connectivity in verbal fluency and deactivation task-related networks was significantly more enhanced by tDCS to DLPFC than to TPC. In addition, DLPFC tDCS increased performance on the phonemic fluency task, after adjusting for baseline phonemic performance. CONCLUSIONS: These findings provide evidence that tDCS to specific brain regions induces changes in large scale functional networks that underlay behavioural effects, and suggest that tDCS might be useful to enhance phonemic fluency in PD.