Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags

Hereditary neuropathies may be misdiagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). A correct diagnosis is crucial for avoiding unnecessary therapies and access genetic counseling. We report on nine patients (seven men, mean age 49.2 ± 16.1) diagnosed with and treated as CIDP, in whom mutations or variants of unknown significance (VUS) in genes associated with hereditary neuropathies were reported. All underwent neurological and neurophysiological examination, eight also cerebrospinal fluid (CSF) analysis. In 4/9, nerve ultrasound and/or MR‐neurography were performed. All the patients complained of progressive upper or lower limbs sensory‐motor symptoms, with heterogeneous disease duration (1‐34 years, mean 8.6 ± 10.8). Neurophysiology showed demyelinating signs in seven patients, mixed findings with predominant axonal damage in two patients. Neuroimaging disclosed diffuse abnormalities at proximal and distal segments. Molecular screening showed PMP22 duplication in two patients, mutations in the MPZ, EGR2, and GJB1 genes were reported in each of the remaining patients. The two patients with mixed neurophysiological findings had p.Val30Met mutation in the transthyretin gene. Two patients had VUS in the MARS and HSPB1 genes. Four patients had partial response to immunomodulant therapies, and CSF and neurophysiological features suggesting an inflammatory condition concomitant with the hereditary neuropathy. Hereditary neuropathy may be misdiagnosed with CIDP. The most common pitfalls are CSF (high protein levels and oligoclonal bands), incorrect interpretation of neurophysiology, and transient benefit from therapies. Neuroimaging may be helpful in cases with atypical presentations or when severe axonal damage complicate the neurophysiological interpretation.     

Diagnosing acute encephalitis in patients with hematological disorders: caveats and pitfalls

Journal of NeuroVirology - The aim of this study was to review the quality of the diagnostic work-up for acute encephalitis carried out at our center in a cohort of patients with hematological...     

Sleep slow oscillations favour local cortical plasticity underlying the consolidation of reinforced procedural learning in human sleep

We investigated changes of slow‐wave activity and sleep slow oscillations in the night following procedural learning boosted by reinforcement learning, and how these changes correlate with behavioural output. In the Task session, participants had to reach a visual target adapting cursor's movements to compensate an angular deviation introduced experimentally, while in the Control session no deviation was applied. The task was repeated at 13:00 hours, 17:00 hours and 23:00 hours before sleep, and at 08:00 hours after sleep. The deviation angle was set at 15° (13:00 hours and 17:00 hours) and increased to 45° (reinforcement) at 23:00 hours and 08:00 hours. Both for Task and Control nights, high‐density electroencephalogram sleep recordings were carried out (23:30?19:30 hours). The Task night as compared with the Control night showed increases of: (a) slow‐wave activity (absolute power) over the whole scalp; (b) slow‐wave activity (relative power) in left centro‐parietal areas; (c) sleep slow oscillations rate in sensorimotor and premotor areas; (d) amplitude of pre‐down and up states in premotor regions, left sensorimotor and right parietal regions; (e) sigma crowning the up state in right parietal regions. After Task night, we found an improvement of task performance showing correlations with sleep slow oscillations rate in right premotor, sensorimotor and parietal regions. These findings suggest a key role of sleep slow oscillations in procedural memories consolidation. The diverse components of sleep slow oscillations selectively reflect the network activations related to the reinforced learning of a procedural visuomotor task. Indeed, areas specifically involved in the task stand out as those with a significant association between sleep slow oscillations rate and overnight improvement in task performance.     

Prostaglandin D2 synthase modulates macrophage activity and accumulation in injured peripheral nerves

We have previously reported that prostaglandin D2 Synthase (L-PGDS) participates in peripheral nervous system (PNS) myelination during development. We now describe the role of L-PGDS in the resolution of PNS injury, similarly to other members of the prostaglandin synthase family, which are important for Wallerian degeneration (WD) and axonal regeneration. Our analyses show that L-PGDS expression is modulated after injury in both sciatic nerves and dorsal root ganglia neurons, indicating that it might play a role in the WD process. Accordingly, our data reveals that L-PGDS regulates macrophages phagocytic activity through a non-cell autonomous mechanism, allowing myelin debris clearance and favoring axonal regeneration and remyelination. In addition, L-PGDS also appear to control macrophages accumulation in injured nerves, possibly by regulating the blood–nerve barrier permeability and SOX2 expression levels in Schwann cells. Collectively, our results suggest that L-PGDS has multiple functions during nerve regeneration and remyelination. Based on the results of this study, we posit that L-PGDS acts as an anti-inflammatory agent in the late phases of WD, and cooperates in the resolution of the inflammatory response. Thus, pharmacological activation of the L-PGDS pathway might prove beneficial in resolving peripheral nerve injury.     

Systemic and organ involvement in monogenic autoinflammatory disorders: a global review filtered through internists’ lens

Monogenic autoinflammatory disorders (AIDs) are rare diseases driven by cytokine-mediated extraordinary sterile inflammation that results from the activation of innate immune pathways. The clinical hallmark of these diseases is the recurrence of stereotyped episodes of systemic- and organ-specific inflammation; the most common systems involved being the skin, musculoskeletal system, gastrointestinal tract, and central nervous system. The autoinflammatory disorders may have a profound impact on the quality of life of the affected patients, and a delayed diagnosis may lead to severe complications, the most dreadful of which is AA-Amyloidosis. This review gives an overview on the four main AIDs, namely familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, cryopyrinopathies, and mevalonate kinase deficiency, focusing on their clinical phenotype in adults and differential diagnosis, suggesting a diagnostic algorithm, and reviewing the available treatments.