The benign paroxysmal positional vertigo (BPPV) is a vestibular disorder cause of vertigo. The BPPV may be corrected mechanically by repositioning maneuvers but even after successful maneuvers, some patients report residual dizziness for a certain period afterward. Early recognition and treatment might decrease the incidence of residual dizziness in patients with BPPV, especially in those patients with psychiatric comorbidities and in the elderly, lowering the risk of falling. Many pathogenetic hypotheses for residual dizziness are under debate. The purpose of this review was to identify, evaluate and review recent researches about possible causal factors involved in residual dizziness and the implications on clinical practice. A literature search was performed using different databases such as Pubmed and Scopus. The following search terms were used: residual dizziness, otolithic membrane and BPPV. The search found a total of 1192 titles, which were reduced to 963 after a procedure of de-duplication of the found titles. The research was then restricted to an interval of time comprised between 2000 and 2016 for a total of 800 titles. Among these titles, only those including the terms benign paroxysmal positional vertigo were considered eligible for this review. Only publications in English language were taken into consideration and we excluded those with not available Finally, 90 abstracts were obtained and critically evaluated by two different Authors, and additional studies were identified by hand searching from the references of artiche of interest. Only 53 were included in this work.

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber–Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.