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Neuroimmunol Neuroinflammation 2019;6:15 I http://dx.doi.org/10.20517/2347-8659.2019.019 Page 3 of 24

3. The circadian system plays a major role in the aetiology, progression and treatment of
parkinson’s disease: ending an era of “forcing nature” with dopamine replacement

Gregory L. Willis

Bronowski Institute of Behavioural Neuroscience, Woodend, Victoria, Australia

There is an ever increasing body of research demonstrating that the circadian system plays an important
role in the motor and non-motor symptoms of Parkinson’s disease (PD). Historical evidence supporting
this hypothesis can be found in the early work of Parkinson, Charcot and others, whereby the symptoms of
this disease can vary in accordance with the phase of the circadian cycle. More recent work, examining the
role of anatomical substrates of the circadian system, has shown that the retina, hypothalamus and pineal
are important locations whereby underlying functional changes may well contribute to the aetiology of PD.
Equally compelling are the recent preclinical and clinical findings demonstrating that more effective, less
invasive therapeutic intervention may well be achieved if chronotherapeutics target these sub-anatomical
parts of the circadian system. In our exploration these substrates we have identified the retina and the
pineal as two such important locations where chronotherapeutics are most effectively delivered to produce
the optimal therapeutic benefit while minimising adverse side effects. In particular, we will demonstrate
how treatments, such as minute intravitreal injections of anti-PD drugs, produce robust therapeutic effects,
that are normally attributed to deep brain structures. In contrast, the chronotherapeutic intervention
observed in in the disease itself using strategic light therapy, provide additional evidence that circadian
function plays a major role in the aetiology, progression and treatment of PD. It is time for a reappraisal
of the underlying anatomical substrates reflexively attributed exclusively to the Nigro-striatal dopamine
system. It is time to sojourn that endless search for the magic bullet of dopamine replacement and pursue
the highly significant, but less invasive, contribution of chronotherapeutics in correcting this disorder.

4. Multicentric cryptococcomas mimicking neoplasia

Adrian Kelly

George Mukhari Academic Hospital & Sefako Makgatho Health Sciences University, Ga-rankuwa, Pretoria,
South Africa

Fungal mass lesions in the central nervous system are, as a group, extremely rare. In this group,
cryptococcomas are the most commonly seen and are often included in the differential diagnosis of the
multicentric space occupying lesions in immunocompromised hosts. While crypococcomas are known to
occur in both healthy and immunocompromised individuals, they are more commonly seen in the latter
where Cryptococcus neoformans is the typical agent. This contrasts the species seen in immunocompetent
hosts where Cryptococcus gatti occurs more commonly.

These lesions are commonly 3-10 mm in diameter and occur in the basal ganglia due to the organism
spreading via the Virchow-Robbins spaces surrounding the small perforator vessels as part of contiguous
spread from a basal meningitis. Although most frequently associated with HIV infection, patients with
chronic renal disease, vascular conditions, hepatitis B or C, alcoholism, diabetes mellitus, and oncological
diseases may also succumb to this infection and present with cryptococcomas.