Hereditary systemic angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy.

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migraine-like headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy. No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma.

AIM: To compare the plasma levels of endothelin-1 (ET-1) between patients with primary open angle glaucoma with visual field progression despite normal or normalised intraocular pressure and patients with stabile visual fields in a retrospective study. METHODS: The progressive group consisted of 16 primary open angle glaucoma patients and the group with stable visual field consisted of 15 patients. After a 30 minute rest in a supine position, venous blood was obtained for ET-1 dosing. Difference in the plasma level of ET-1 between two groups was compared by means of analysis of covariance (ANCOVA), including age, sex, and mean arterial blood pressure as covariates. RESULTS: ET-1 plasma levels were found to be significantly increased in patients with deteriorating (3.47 (SD 0.75) pg/ml) glaucoma when compared to those with stable (2.59 (SD 0.54) pg/ml) visual fields (p = 0.0007). CONCLUSIONS: Glaucoma patients with visual field progression in spite of normal or normalised intraocular pressure have been found to have increased plasma endothelin-1 levels. It remains to be determined if this is a secondary phenomenon or whether it may have a role in the progression of glaucomatous damage.

Increased endothelin-1 plasma level in young adults with retinal vascular occlusive diseases.

BACKGROUND: Vascular occlusive diseases are usually seen in the elderly but can occur even in younger patients without arteriosclerosis. We assume a vascular dysregulation as a underlying pathogenetic mechanism. PATIENTS AND METHODS: In a prospective study we analysed the clinical findings of six patients under 55 years of age, three men with retinal vein occlusions and three women with branch retinal arterial obstructions. They were examined for signs of a vascular dysregulation and the endothelin-1 (ET-1) plasma level was measured. RESULTS: In all patients the ET-1 plasma level was markedly elevated. The mean value (3.72 +/- 0.8 pg/ml) was significantly increased compared to normal values for that age (1.52 +/- 0.24 pg/ml; p < 0.001). In all cases an increased tendency for vascular dysregulation could be demonstrated in nailfold capillaroscopy. Furthermore, frequent coldness of the extremities was mentioned by every patient and migraine was mentioned by four patients whereas neither changes of the vessels in carotis and ophthalmica region nor disturbances in the haemostasis and fibrinolysis could be found. CONCLUSIONS: All six patients with vascular occlusive diseases occurring before the age of 55 had a vascular dysregulation and increased ET-1 plasma levels. A relationship between the vascular dysregulation and the vascular occlusive diseases is therefore likely.

Susac syndrome: a vasospastic disorder?

PURPOSE: The Susac syndrome is a microangiopathy that leads to visual symptoms, hearing loss and neurological symptoms. CASE REPORT: We report on a young woman suffering from this syndrome who also presented the following signs and symptoms typical of a vasospastic syndrome; 1) a history of cold hands, low blood pressure and migraine; 2) a typical alteration of conjunctival vessels; 3) prolonged flow arrest time after cooling in nailfold capillaromicroscopy; 4) increased resistivity in the orbital vessels measured by color Doppler imaging; and 5) an increased plasma level of endothelin-1. CONCLUSIONS: We postulate that the Susac syndrome is a manifestation of the vasospastic syndrome.

Pupillary examination with infrared consumer videocamera.

BACKGROUND: Pupillary observation in the dark is always a problem in a general ophthalmological practice or an outpatient clinic without specialized equipment. We present two methods for observation of the pupils in darkness: 1) illumination of the pupils with the skiascope as a routine examination and 2) infrared observation of the pupils with a consumer digital video camera. METHODS: (1) Pupillary reactions are observed with the skiascope/retinoscope, the observation beam of the device focused to infinity and documented with a video camera. (2) Infrared observation of the pupils was performed with a digital consumer video camera, allowing observation of the pupillary reaction in darkness. After recording, video sequences of interest were transferred to a personal computer and the still images of interest extracted. RESULTS: In everyday clinical routine, observation of the pupillary reaction with the skiascope/retinoscope proves as a reliable tool with a large bandwidth of illumination and a high contrast between pupil and surrounding area. The infrared video camera allows an excellent visualization of the pupillary reflex in darkness. The transfer of the video sequences to a personal computer proved to be simple and single images can easily be chosen. CONCLUSION: Observation of the pupillary reflex with the skiascope proved a useful tool that is available in practically every ophthalmological office. Use of the infrared digital consumer video camera (available at low prices) is a highly sophisticated tool for observation and documentation of pupillary reflex in darkness.

Increased endothelin-1 plasma levels in patients with multiple sclerosis.

OBJECTIVE: We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients. MATERIALS AND METHODS: A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MS were compared to 20 age- and sex-pair-matched healthy subjects. RESULTS: The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease. CONCLUSIONS: The plasma ET-1 level is markedly and significantly increased in patients with MS. Neither the cause of such an increase nor the pathogenetic role is known.

Nitric oxide production by isolated human and porcine ciliary processes.

BACKGROUND: In the kidney, the trachea, and the colon, nitric oxide (NO) can modulate transepithelial fluid transport. This study investigates whether isolated human and porcine ciliary processes produce NO. METHODS: Porcine ciliary processes and iris were used either fresh or thawed after storage at -70 degrees C. Post-mortem (8-12 h) human ciliary processes were used thawed after storage at -70 degrees C. NO was measured by placing a nafion-coated polymeric porphyrinic microsensor (differential pulse voltammetry) on the surface of the tissue. Measurements were conducted in the absence or in the presence of the NO formation inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.2 mM, 1 mM) or its biologically inactive D-enantiomer N(G)-nitro-D-arginine methyl ester (D-NAME; 1 mM). RESULTS: NO concentrations in porcine ciliary processes (1.27+/-0.25 microM) were higher (P=0.001) than those in the iris (0.00+/-0.02 microM) and were significantly (P<0.001) decreased by L-NAME (fresh specimen). From thawed porcine ciliary processes, NO concentrations measured (1.85+/-0.47 microM) were not significantly different (P=0.16) from those measured in fresh specimen and were also reduced (P <0.001) by L-NAME, but not by D-NAME. In human ciliary processes, NO concentrations measured (0.08+/-0.11 microM) were somehow lower but were again decreased (P<0.001) by L-NAME (thawed specimen). CONCLUSION: Reflecting the biological activity of a nitric oxide synthase, isolated human and porcine ciliary processes produce NO.

Spontaneous calcium-independent nitric oxide synthase activity in porcine ciliary processes.

In the cornea, iris, retina, and ciliary processes of porcine eyes the nitric oxide synthase (NOS) activity was assayed by measuring the transformation of L-[U-14C]-arginine into L-[U-14C]-citrulline: (1) in the absence or presence of the calcium-chelator, ethylene glycol tetra acetic acid (EGTA), and (2) in the presence of EGTA and the false precursor of L-arginine, NG-nitro-L-arginine methyl ester (L-NAME). In the retina and the iris a high calcium-dependent NOS activity was present, while in the cornea the activity was relatively low. In these three tissues no significant calcium-independent NOS activity was detected. In contrast, a marked calcium-independent NOS activity, but no calcium-dependent NOS activity, was found in the ciliary processes. The presence of a spontaneous calcium-independent NOS activity in the ciliary processes suggests that nitric oxide (NO) production is highly regulated in this tissue.