Accumulating evidence suggests that sporadic Parkinson's disease has a long prodromal period during which several non-motor features develop, in particular, impairment of olfaction, vagal dysfunction and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexus of the stomach. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (i) nasal, with anterograde progression into the temporal lobe; and (ii) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and, via transsynaptic transmission, reach the preganglionic parasympathetic motor neurones of the vagus nerve. This would allow retrograde transport into the medulla and, from here, into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed, and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sporadic Parkinson's disease is pathogenic access to the brain through the stomach and nose - hence the term 'dual-hit'.

Maria was distraught after reading about the 'potential' epidemic, yet to happen, and the horror stories on Facebook needing reassurance and certainty about what she should do. She requested an urgent appointment to review her treatment plan. Maria was a 26-year-old woman with relapsing multiple sclerosis who had recently experienced brainstem relapse with double vision and ataxia despite treatment with pegylated interferon-beta for the last 18 months. A brain MRI performed one month prior had shown 16 new T2 lesions, four of which were enhancing. One of the enhancing lesions was at the pontomedullary junction and was certainly the cause of her relapse. Treatment was to be escalated to ocrelizumab with the first dose in a week's time. In view of the emerging coronavirus pandemic, she was questioning whether or not she should go ahead with ocrelizumab. This was despite only a handful of confirmed COVID-19 cases in the country and none in her town and region.If this scenario sounds plausible what should neurologists do? Human coronaviruses are predominantly associated with respiratory tract infections and includes those that cause severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and now the COVID-19 pandemic.In an uncertain world, where we do not have a clear evidence-base, you often have to default to scientific principles, rather than using the wisdom of the crowd. Not surprising, with Italy being one of the epicentres of the COVID-19 epidemic, the Italian society of neurology or SIN (Società Italiana di Neurologia) broke cover first producing recommendations on the management of patients with MS during the COVID-19 epidemic (see Box 1). The SIN guidelines provide relatively straightforward, and one could argue arbitrary, advice on how to manage patients with MS in the short-term, but do not address supervision of these patients in the intermediate or long-term especially those with highly active MS. If the public health measures being taken flatten the peak of the epidemic, but extend its tail, the problem of community-acquired SARS-CoV2 infection and COVID-19 may be with us for many months and potentially years. Are the SIN guidelines compatible with the best interests of our patients or a knee-jerk response to an undefined problem that may not be a problem at all?

These results indicate that olfactory function is differentially impaired or preserved in distinct parkinsonian syndromes and that it might also have some value as a diagnostic pointer. Thus, preserved or mildly impaired olfactory function in a parkinsonian patient is more likely to be related to atypical parkinsonism such as MSA, PSP or CBD, whereas markedly reduced olfaction is more suggestive of IPD.

Our patients with early PD have a frequent and severe olfactory deficit that correlates with disease severity, symptom duration and DaTSCAN but not EGM. The sensitivities of UPSIT and DaTSCAN are high at 86% and 92%, respectively. Although DaTSCAN is superior for 'localization', UPSIT is considerably 'cheaper', and neither is disease specific. EGM threshold impairment in PD is independent of the smell deficit, and probably signifies advanced disease.

It has been known for over 30 years that olfactory function is disordered in idiopathic Parkinson's disease (IPD). The severity and partial specificity of anosmia was not realized until recently, with the advent of more detailed analysis and sophisticated measurement. The olfactory vector hypothesis suggests that the causative agent for IPD enters the brain via the nasal route, but the reason for olfactory dysfunction may be more subtle. Evidence for olfactory disturbance is reviewed from pathological, psychological, neurophysiological and genetic stand-points. It is proposed that the initial causative event in IPD may start in the rhinencephalon (olfactory brain) prior to damage in the basal ganglia.