Spondylodiscitis in ankylosing spondylitis, inflammation or trauma? A description of six cases.

An uncommon, but well recognised complication of Ankylosing Spondylitis (AS) is spondylodiscitis, a destructive discovertebral lesion also called the Andersson lesion. We describe six cases, with variable clinical presentation and radiological appearance. Two had multiple lesions, in one patient spondylodiscitis was the presenting symptom of AS. None had a history of even a minor trauma. Prognosis was good with conservative treatment including NSAID's, rest, and physiotherapy. In two cases histopathology was studied and suggested sterile inflammation as the main etiologic factor. The literature is reviewed regarding the mechanisms that may contribute to these lesions: mainly inflammatory like increasing enthesopathy or mainly mechanical like pseudoarthrosis about a fracture site. It may be that both mechanisms can result in similar destructive intervertebral disc lesions.

Tophus-like cholesterol nodules in 2 patients with rheumatoid disease.

We describe 2 patients, both with rheumatoid disease, with tophus-like nodules that contained cholesterol crystals. A tophus-like cholesterol nodule had developed in a tendon sheath of the left little finger of one. The other presented with multiple tophus-like nodules on his left elbow and both forefeet. We discuss the etiology and pathogenesis of crystalline deposits of cholesterol. Nodules at sites of local pressure in patients with rheumatoid arthritis may be deposits of cholesterol crystals.

[Spondylodiscitis in Bechterew's disease; inflammation or trauma? Description of 6 patients]. / Spondylodiscitis bij de ziekte van Bechterew; ontsteking of trauma? Een beschrijving van 6 patiënten.

OBJECTIVE: To study the prevalence and nature of sterile spondylodiscitis in patients suffering from ankylosing spondylitis. DESIGN: Descriptive. SETTING: Department of Rheumatology, Medisch Spectrum Twente, Enschede, the Netherlands. METHOD: Of all ankylosing spondylitis patients suffering from sterile spondylodiscitis, the medical histories and the radiological and histological findings were analysed. RESULTS: Among about 400 patients, 6 cases of sterile spondylodiscitis were found; 4 men and 2 women. The mean time lapse between diagnosis of ankylosing spondylitis and onset of spondylodiscitis symptoms was 7 years; in I patient discitis was the first symptom. Discitis changed the nature of the backache: it worsened during exercise and improved on resting. There was no history of trauma. Symptomatic and asyptomatic radiological abnormalities were seen at the same time in 2 patients. Symptoms disappeared 3-36 months after start of conservative treatment. Histological examination was performed in 2 cases and showed inflammatory changes. CONCLUSION: Spondylodiscitis in ankylosing spondylitis has a highly variable presentation and in general a good prognosis. Our findings support an inflammatory rather than a traumatic pathogenesis.

Treatment of diabetic autonomic neuropathy with an aldose reductase inhibitor.

To evaluate the effects of the aldose reductase inhibitor Ponalrestat (Statil) on diabetic autonomic neuropathy, a double-blind placebo controlled trial was carried out on a group of 34 diabetic patients with documented cardiac autonomic neuropathy. After a 4-week, placebo run-in period, patients were randomised for treatment with 600 mg Statil or placebo for another 24 weeks. Moreover, the reliability of the autonomic nerve function tests was investigated by comparing the results at onset and at week 4. Fifteen patients treated with Statil and 12 with placebo completed the study. Neither symptom scores nor cardiovascular reflexes, pupil reflexes and skin vasomotor reflexes improved after Statil therapy, which led us to conclude that Statil is not effective in the treatment of diabetic autonomic neuropathy. Reliability coefficients for cardiovascular reflexes and pupil reflex showed high values, ranging from 60% to 80%. Therefore these methods are recommended in future therapy trials.

Pupillary light reflex latency in patients with multiple sclerosis.

In 46 patients with definite multiple sclerosis (MS) the direct and indirect pupillary light reflex latency (PLRL) and visual evoked potential (VEP) latency of the P100 were measured for each eye separately. The PLRL was measured at both photopic and scotopic illuminance level, using an infrared light reflection technique (IRIS). On average the PLRL increased at the scotopic illuminance level as compared with the photopic (P less than 0.0001). An abnormal VEP was found in 80.4% of the patients, while 26.1% and 29.7% had an abnormal direct PLRL at photopic and scotopic illuminance level respectively. No correlations were found between PLRL and VEP or visual acuity. In MS patients with unilateral optic signs (optic neuritis or slowly progressive visual failure) a relative prolonged PLRL could be demonstrated in the symptomatic eye as compared to the asymptomatic eye. Based on formulae to quantitate relative afferent and efferent impairments of the pupillary pathway, it is demonstrated that prolonged PLRL measurements mainly reflect the nerve conduction in the efferent pupillary pathway.

Evaluation of the visual system in multiple sclerosis: a comparative study of diagnostic tests.

In 22 patients with clinically definite multiple sclerosis (MS) who were without visual symptoms and had a visual acuity of at least 1.0 in both eyes at the time of measurement, the following tests were performed to detect subclinical lesions in the visual system: visual evoked potential (VEP), contrast sensitivity test (CS), flight of colours test (FOC), colour vision test (Ishihara plates) (CV) and the pupillary light reflex (PLR). VEP was abnormal in 81.8%, CS in 72.7%, FOC in 36.4%, CV in 31.8%, and PLR in 52.3% of the patients. VEP and CS together were most sensitive: combining these techniques subclinical lesions of the visual system were detected in 90.9% (20/22) of these asymptomatic patients.

Cardiovascular autonomic function in multiple sclerosis.

In this study blood pressure (BP) and heart rate (HR) responses to standing and HR responses to deep breathing were assessed in 34 patients with clinically definite multiple sclerosis (MS) and 63 healthy subjects. Normal ranges, which were clearly age related for both HR responses, were obtained. The BP response to standing was abnormal in 13% of the MS patients, these patients demonstrating significant postural hypotension. The HR response to standing was abnormal in 28% of the MS patients, with a normal initial increase in heart rate and a significantly reduced reflex bradycardia. On deep breathing 36% of MS patients showed abnormal HR changes. The resting HR did not differ between both groups. Abnormalities of one or more tests were found in 53% of the MS patients. No relationship was found between abnormal cardiovascular autonomic responses and the symptoms, duration, severity and progression of the disease. Based on clinical and magnetic resonance imaging findings no indications were found for localisation of the autonomic disturbances in the brainstem. It is suggested that at least a part of the cardiovascular autonomic lesions in MS is located outside the brainstem, i.e. in supramedullary reflex pathways or in the spinal cord.

[Angioedema caused by enalapril]. / Angio-oedeem ten gevolge van enalapril.

Since 1984 25 cases of enalapril induced angioedema have been reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs. Two patients with enalapril induced angioedema are described. The pathophysiological mechanism of this potentially life-threatening adverse effect is probably not a direct allergic response to the drug itself. Enalapril inhibits angiotensin converting enzyme, which not only metabolizes angiotensin I but also bradykinin and 'substance P'. Bradykinin and 'substance PH may then accumulate and cause angioedema in a direct or indirect way. It is of great importance that instances of oropharyngeal swelling are considered a possible result of an adverse reaction to ACE-inhibitors.

The cause of increased pupillary light reflex latencies in diabetic patients: the relationship between pupillary light reflex and visual evoked potential latencies.

In 42 diabetic patients the relationship between the latency of the pupillary light reflex and the pattern reversal visual evoked potential (P100) was examined. Fifty-five percent of diabetic patients had pupillary light reflex latencies above the normal range. In 19% the visual evoked potentials were prolonged when compared to the normal range. Latencies of pupillary light reflexes and VEPs showed no correlation. There was a minimal correlation between the presence of retinopathy and prolongation of both the pupillary light reflex and the visual evoked response latency (kappa coefficients respectively: 0.31, P less than 0.01 and 0.36, P less than 0.02). The presence of an increased pupillary light reflex latency was positively correlated with a reduced respiratory sinus arrhythmia (kappa coefficient: 0.58, P less than 0.0001). Increased VEP latencies showed no correlation with signs of cardiovascular autonomic neuropathy. We conclude that the afferent optic pathway can be affected in diabetic patients. However, prolongation of pupillary light reflex latency in diabetic patients is primarily due to an efferent pupillary defect and represents parasympathetic dysfunction.

Assessment of pupillary light reflex latency and darkness adapted pupil size in control subjects and in diabetic patients with and without cardiovascular autonomic neuropathy.

Increased pupillary light reflex latencies were found more often than a reduced darkness pupil size in diabetic patients with and without abnormal cardiovascular reflexes. This finding suggests that parasympathetic pupillary dysfunction precedes sympathetic pupillary denervation in diabetic autonomic neuropathy.

Spectral analysis of spontaneous heart rate variation in diabetic patients.

In 28 diabetic patients and 62 control subjects spectral analysis of spontaneous beat-to-beat RR interval variations was performed. The spectral analysis focused on the dominant frequency of the mid-frequency band (0.04-0.12 Hz) or baro-oscillatory phenomenon (BOP). Compared with control subjects the dominant frequency of the BOP (BOP frequency) in the diabetic patients was lower (p less than 0.001), and the difference increased with age. The shift of the BOP frequency was positively correlated with the reduced variation in heart rate during deep breathing (r = 0.80, p less than 0.001) in the diabetic patients. These findings indicate that determination of the BOP frequency is a useful method for assessing cardiovascular autonomic function, supplementary to the known cardiovascular reflex tests. Measurement of the BOP frequency has the advantage that no active patient co-operation is required.

Autonomic and somatic peripheral nerve function and the correlation with neuropathic pain in diabetic patients.

Pupillary and cardiovascular autonomic functions were examined in 25 diabetic patients with and 25 diabetic patients without painful neuropathy. There were no significant differences between the groups with regard to age, duration of diabetes or glycaemic control. Vibratory perception, reflecting peripheral large fibre function, was more severely disturbed in the symptomatic group (P = 0.003). Thermal discrimination thresholds (TDTs), reflecting somatic small fibre function, were abnormal in all symptomatic patients and the difference between patients with and without symptoms was more pronounced (P less than 0.0001), than for large fibre function. The latency of the constriction reaction of the pupil (parasympathetic function) was prolonged in 17 symptomatic patients and in 6 patients without pain; it proved to be significantly more prolonged in the group with painful neuropathy (P = 0.001). Cardiovascular autonomic neuropathy was present in 29 patients, especially in patients with painful neuropathy (22 in the group with painful neuropathy, 7 in the group without pain). There was a significant correlation between results of TDT and respectively pupillary and cardiovascular autonomic function tests (kappa coeëfficient: 0.63 and 0.56, respectively, P less than 0.0001). We conclude that autonomic dysfunction is often present in patients with painful neuropathy. However, thermal sensory dysfunction is better correlated with the presence of symptoms than cardiovascular and pupillary autonomic dysfunction.

Observations on the lesion site in the Miller Fisher syndrome: presentation of a case including CT and MRI.

Debate about the lesion site in the Miller Fisher syndrome is still going on. We studied a patient with features of the Miller Fisher syndrome in whom arguments for both central and peripheral nervous system dysfunction were found.

Efficacy and acceptance of two intensified conventional insulin therapy regimens: a long-term cross-over comparison.

The efficacy and acceptability of multiple daily insulin injections (three preprandial injections of short-acting insulin (NovoPen) plus once daily extended-acting insulin) were compared with those of twice daily injections of short- and intermediate-acting insulin. Sixteen Type 1 diabetic patients participated in a cross-over study (6-month treatment periods). Total areas under 24-h plasma free insulin curves, assessed at the end of each study period, were not significantly different, but a greater area under this curve was found for the pen-injector regimen from 1200 to 1600 h (150 +/- 15 (SE) vs 106 +/- 7 mU l-1 h, p less than 0.01). Home blood glucose profiles showed significantly lower values with pen-injector therapy after lunch (7.1 +/- 0.6 vs 8.4 +/- 0.4 mmol l-1, p = 0.05) and before and after dinner (6.4 +/- 0.6 vs 8.8 +/- 0.5 mmol l-1, p less than 0.005, and 7.5 +/- 0.7 vs 9.4 +/- 1.1 mmol l-1, p less than 0.05). Mean daily blood glucose concentration was also lower (7.1 +/- 0.4 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05). HbA1, fructosamine, hypoglycaemic reactions, and body weight were not significantly different. Thirteen patients decided to continue with pen-injector therapy at the end of the study.

Pupillary light reflex and quantitative sensory and motor neural function tests in diabetic patients.

In 29 diabetic subjects with or without symptoms of diabetic peripheral and autonomic neuropathy, the association between the pupillary light reflex (the latency of the constriction of the pupil) and various sensory and motor neural measurements, duration of diabetes and quality of glycaemic control was evaluated. Compared with normal subjects the latency of the constriction reaction of the pupil was significantly prolonged in the group of diabetics (mean +/- SEM: 236.3 +/- 5.8 ms versus 210.5 +/- 3.7; P less than 0.001). Thermal discrimination thresholds were positively correlated with the latency of the constriction reaction of the pupil (r = 0.43, P less than 0.025). Vibratory perception threshold, motor nerve conduction velocity of the peroneal nerve, H-M interval of the Hoffmann reflex and duration of diabetes were not correlated with the constriction latency, whereas glycaemic control showed a weak correlation. It is concluded that there may be a relationship between autonomic (parasympathetic) pupillary dysfunction and peripheral small nerve fibre dysfunction.

Decreased scattering coefficient of blue sclerae.

The optical scattering properties of blue and normal sclerae were studied with a fiber optic scattering monitor. The scattering was clearly reduced in two osteogenesis imperfecta patients with blue sclerae, and low normal in one osteogenesis imperfecta patient without blue sclerae.