Immune aging is best known for its immune defects that increase susceptibility to infections and reduce adaptive immune responses to vaccination. In parallel, the aged immune system is prone to autoimmune responses and many autoimmune diseases increase in incidence with age or are even preferentially encountered in the elderly. Why an immune system that suboptimally responds to exogenous antigen fails to maintain tolerance to self-antigens appears to be perplexing. In this review, we will discuss age-associated deviations in the immune repertoire and the regulation of signaling pathways that may shed light on this conundrum.

PURPOSE:

To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes.

DESIGN:

Prospective, multicenter, observational case series.

PARTICIPANTS:

A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy. TESTING: Magnetic resonance imaging (MRI) of the brain.

MAIN OUTCOME MEASURES:

Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment.

RESULTS:

Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64).

CONCLUSIONS:

In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Giant cell arteritis and polymyalgia rheumatica are common reasons for prescribing long-term glucocorticoid therapy. Glucocorticoids efficacy in these patients is rapid and undeniable, but it is often overshadowed by adverse events, appearing more or less early during treatment course. These adverse events are usually minor but some of them may be life threatening. Because of the absence of randomized, controlled trials comparing glucocorticoids to placebo in this indication and in this aged population, it is difficult to precise the role of corticosteroids in the occurrence of some complications that can also be precipitated by the disease itself (e.g., vascular complications) or related to aging. In this context, analysis of the crude morbidity and mortality can help in anticipating the potential problems that these patients will encounter. In addition, the long duration of glucocorticoid exposure should prompt physicians to be particularly vigilant regarding some adverse events that are minimally symptomatic on the short term but have a major long-term impact.

Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood--brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nerve system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide recommendations on how to effectively promote the field in order to create innovative diagnostic tools to predict the pathology and develop more efficient treatment approaches tailored to the person.

Cytomegalovirus (CMV) infection is generally associated with significant immunosuppression. Cellular immunity is particularly important and corticosteroid treatment increases the risk of CMV infection substantially. Immunocompetence generally decreases with age, older patients are at higher risk for developing CMV disease than are younger patients. CMV infection in the immunocompetent adults is quite rare. Esophagitis is the second most common gastrointestinal manifestation of CMV infection after colitis. Herein, we present three cases of giant cell arteritis who developed CMV esophagitis after various periods of corticosteroid treatment. CMV infection should be included in the differential diagnosis of GI disease in immunocompromised patients, and the clinician should pursue appropriate diagnostic and therapeutic interventions aggressively.

Intermittent claudication of the lower extremities is a common symptom described in older patients with atherosclerotic peripheral arterial disease. Peripheral arterial disease due to atherosclerosis is known to be associated with a higher risk of myocardial infarction, stroke and all-cause mortality. However, if intermittent claudication appears in a younger group of patients or older patients in absence of traditional risk factors for atherosclerosis such as smoking, dyslipidemia, arterial hypertension and diabetes mellitus other causes than atherosclerosis must be considered. These conditions include vasculitides, fibromuscular dysplasia, cystic adventitial disease, excentric vascular compression by tumor, popliteal artery entrapment syndrome, trauma or dissection. Vasculitides present a heterogenous group of disorders characterized by inflammatory destruction of blood vessels. Although often not a leading symptom intermittent claudication could be a part of a clinical picture in giant-cell arteritis, Takayasu´s arteritis, Buerger´s disease, polyarteritis nodosa or Behçet disease. Limb claudication is usually of rapid onset, progressive and bilateral. Each of the mentioned vasculitides is specific in ethiology and clinical manifestation with a variable prognosis for the patient. Increased awareness of the presence of different causes of limb claudication and their early diagnosis with a prompt initiation of appropriate treatment may help to avoid clinical progression that can lead to vascular surgery or even limb loss (Ref. 37). Keywords: intermittent claudication, giant-cell vasculitides, variable clinical picture.

Giant cell arteritis (GCA) is a rare disease among Asians. Arteritic anterior ischemic optic neuropathy, which accompanies GCA, has not yet been reported in Koreans. Diagnosis of GCA is difficult if typical symptoms other than visual loss are absent. Here, we report a case of an 83-year-old Korean woman presenting with sudden visual loss in both eyes (oculus uterque, OU). Her visual acuities included perception of light in the right eye (oculus dexter, OD) and perception of hand motion in the left eye (oculus sinister, OS). The results of the Hardy-Rand-Rittler test and Ishihara test showed total dyschromatopsia OU. The Goldmann perimetry test revealed a total field defect OD and paracentral island OS. Fundus examination revealed chalky-white disc swelling OU. Other systemic symptoms and signs were unremarkable. The erythrocyte sedimentation rate, C-reactive protein and platelet count were highly elevated. Temporal artery biopsy revealed multiple lymphocytes and multinucleated giant cells in the arterial media layer. To our knowledge, this is the first report of GCA in a Korean that has been confirmed with temporal artery biopsy. In conclusion, silent GCA can occur in Koreans, and hence, elderly patients presenting with chalky-white disc swelling, and corresponding laboratory findings must be evaluated for GCA.

The epidemiology of systemic vasculitides differs between Japan, Europe and North America. Takayasu's arteritis occurs frequently in Japan, unlike giant cell arteritis. A collaborative international study comparing the epidemiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis between Japan and the United Kingdom (UK) demonstrated that microscopic polyangiitis and myeloperoxidase-ANCA were more common in Japan whereas granulomatosis with polyangiitis and pronase 3-ANCA were more common in the UK. These differences may be attributed to differences in latitude and genetic backgounds. These findings provide useful information on the aetiology and pathogenesis of primary systemic vasculitides in various geographical regions.