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J Ophthalmic Vis Res. 2011 Oct; 6(4): 284–308.
 
PMCID: PMC3306114
PMID: 22454751
CNS Diseases and Uveitis
Pia Allegri, MD,1 Roberto Rissotto, MD,2 Carl P. Herbort, MD, PD, FMER, FEBO,3,4 and Ugo Murialdo, MD1


Abstract
A number of inflammatory, infectious, neoplastic and idiopathic disorders affect the eye and the central nervous system (CNS) concurrently or at different time frames. These conditions pose a diagnostic challenge to the clinician since they may present with similar ocular and neurological manifestations. The purpose of this review is to describe major neurological syndromes including multiple sclerosis, Vogt-Koyanagi-Harada disease, other autoimmune syndromes, and several infectious diseases which may affect the eye. This article may serve as a guide for the diagnosis and treatment of such disorders. It should be noted that these conditions have been viewed from a neurologist’s perspective thereby neurologic involvement is stressed.
Keywords: CNS Inflammatory and Infectious Diseases, Eye Inflammatory and Infectious Diseases, Uveitis

INTRODUCTION

The frequent concurrence of uveitis and central nervous system (CNS) diseases may be derived from the common embryogenic developmental pathway of the posterior segment and the CNS. Analogies between the blood brain barrier and the blood retinal barrier, and “immune privilege” involved in the prevention and blockage of noxious immune system reactions both in the eye and CNS also reflect the common origin of these organs. A North-American review1 revealed that about 8% of individuals suffering from uveitis have associated neurological symptoms, however “neurological” patients seldom have uveitis, probably because neurologists usually consider the CNS disease as the leading condition requiring treatment.

Many CNS disorders affect the posterior segment of the eye. Despite their heterogeneous origin (demyelinating, infectious, inflammatory-autoimmune and neoplastic), upon which the most recent classification is based, these diseases have a single functional unit as their target, represented by the CNS and the eye.

Such pathogenetic associations may underlie variability in prevalence related to ethnicity. For instance Behçet disease, which is rare in the USA (0.3% of uveitic entities)1, is very frequent in the Turkish population (more than 30%)2,3.

Apart from these considerations, we also have to point out that, the most represented patients in Smith’s work was a group of people suffering from CNS disease of unknown origin (meningitis and myelitis) or peripheral nervous system (PNS) disease (angiitis).1

From an etiological point of view, the two broadest and most recent surveys from the USA (1,450 patients)1 and Europe (Austria, 1,973 subjects)4, are not univocal regarding the etiology of conditions described above. The American analysis shows that about 8% (115/1,450 subjects) with neurological diseases had associated uveitis among which demyelinating disorders, Vogt-Koyanagi-Harada (VKH) disease and lymphomas were more frequent. On the other hand, the European study showed that only 2.6% (52/1,973 patients) had a neurological/uveitis related disease, the most prevalent of which were demyelinating, VKH, bacterial, Behçet’s and lymphomatous disease.

This review will discuss major entities which present with neurological and ocular inflammatory diseases.

West Nile Virus

West Nile virus (WNV) infection is a mosquito-borne disease widely distributed in all continents. Since 1999, when the first outbreak of WNV encephalitis occurred in New York city, it has had an impressive spread, representing a recent example of geographical evolution of a disease formerly restricted to specific areas.20

WNV, similar to other arbovirus (flavivirus family) transmitted infections such as dengue, yellow fever and Japanese encephalitis, shares the common feature of neuro-invasiveness with grey matter affinity, with loci of involvement in the cortex, basal ganglia, brainstem, cerebellum and spinal cord. Less than 1% of infected individuals develop severe neuro-invasive diseases which can be classified into three major but sometimes overlapping, clinical syndromes: meningitis, encephalitis and acute flaccid paralysis.21

Meningitis has the usual manifestations: fever, headache and neck stiffness. Encephalitis shows focal symptoms related to the site of involvement such as epilepsy (cortex), tremor and involuntary movements (basal ganglia), parkinsonism (substantia nigra) and ataxia (cerebellum). Encephalitis incurs severe sequelae and a high incidence of death. Acute asymmetric flaccid paralysis, similar to poliomyelitis (a selective lesion in anterior spinal horns), has an unfavourable outcome with variable recovery.

Before the onset of ocular or CNS symptoms, many patients are healthy without any signs of immunosuppression, while some (approximately 20%) complain of mild flu-like symptoms including headache, fever, malaise, gastrointestinal upset, skin rash, neck rigidity and changes in mental status.

Ocular manifestations are uncommon although chorioretinitis may be more frequent than previously reported.22 Bilateral multifocal chorioretinitis with typical clinical and fluorescein angiographic features including linear clusters of oval chorioretinal lesions primarily located in the posterior pole or in the mid-periphery along major retinal vessels, is the most common finding followed by other ophthalmic manifestations such as anterior uveitis, vitritis, retinal vasculitis, and optic nerve involvement (optic neuritis and optic disc swelling).

Detection of WNV–specific IgM in the serum or CSF provides strong evidence of recent infection. IgM usually becomes detectable 8 days after the onset but may become elevated after some months22. Therefore, WNV-IgM may reflect previous infection rather than recent disease. Direct detection of WNV in the CSF, serum or tissue specimens by viral isolation is also of possible diagnostic value. Patients with neuro-invasive disease show lymphocytic pleocytosis in the CSF. MRI is usually normal, but signal modifications may be seen in the basal ganglia, thalamus, brainstem and anterior spinal cord of patients with encephalitis or acute flaccid paralysis.