Ultrastructure study of skin fibroblasts in patients with Ehlers-Danlos Syndrome (EDS): preliminary results.

AIM OF THE STUDY: To investigate, in vivo and in vitro, the fibroblast-to-myofibroblast transition in patients with hypermobile Ehlers-Danlos Syndrome (EDS). To analyze the dermis of patients with classical form of EDS (cEDS) and with hEDS, to identify qualitative and/or quantitative differences in ECM component and ultrastructural changes in collagen. MATERIALS AND METHODS: Seven subjects, aged over 18, two with cEDS and five with hEDS underwent two skin biopsy. One sample was prepared for transmission electron microscopy (TEM), the other for immunofluorescence. The diameter of collagen fibers was measured with TEM. Fibrils were analyzed in four patients: the two with cEDS and two with hEDS. For each patient, the diameter of n=250 collagen fibrils was measured. αSMA was used as specific marker for myofibroblast to highlight their presence in vivo in the skin of patients with hEDS. RESULT: IF observation could not assess an increased expression of αSMA in hEDS patients, which showed no statistical difference compared to classic form patients. The major result from the analysis of TEM images is the clear difference in ECM composition between the two forms of EDS: ECM in hEDS is optically more dense and more prominently composed of elastic fibers. CONCLUSION: Our study provides the following important evidence: 1) the absence in vivo of dermal fibroblasts in patients with hEDS, demonstrated by αSMA negativity; 2) the presence of statistically significant changes in the diameter of collagen fibrils between the classic and the hypermobile forms.

Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG).

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood.

Short-latency scalp somatosensory evoked potentials and central spine to scalp propagation characteristics during peroneal and median nerve stimulation in multiple sclerosis.

Peripheral (cauda-lumbar, wrist-Erb, Erb-cervical) and central (cauda-vertex, cervical-scalp) nervous impulse propagation velocities and times to peroneal and median nerve stimulation were investigated in 34 patients suffering from definite (17 cases), probable (6 cases) and possible (11 cases) forms of multiple sclerosis (MS). In 6 cases short- and intermediate-latency scalp somatosensory evoked potentials to peroneal nerve stimulation were recorded with 'open' (1-5000 Hz, -6 dB) bandpass filters and subsequently digitally filtered through a 'narrow' bandpass (200-5000 Hz, -6 dB). The lumbar response was abnormal in 2.95% of legs, while the Erb response was always within normal limits. The cauda-vertex conduction was altered in 75% of the examined limbs (86.2% definite, 58.3% probable, 63.6% possible MS). Absent scalp responses to peroneal stimulation were often encountered during narrow bandpass recording (54.9%), while a slowed central conduction was less frequent (33.3%). Scalp responses when recorded with open bandpass were always identifiable, being delayed in 3 out of 6 cases. In 5 of these the short-latency wavelets were either absent or showed a prolonged interpeak time even when open filter records were normal. Median nerve SEPs were altered in 60.3% of cases, more frequently because of a delayed scalp response or of a prolonged cervical-scalp conduction time than because of an absent cervical or scalp response. When peroneal and median nerve data were considered together, the rate of abnormality rose to 88.2% of patients. Due to their length, afferent pathways from the lower limb might suffer from a loss of high frequency impulse coding as an early sign of defective impulse propagation.

Effects of intravenously administered L-acetylcarnitine on somatosensory-evoked potentials. Studies of healthy and diseased volunteers with focal cerebral lesions.

The acute effects of intravenously administered L-acetylcarnitine (L-AC) were evaluated in 5 healthy and 20 diseased volunteers (17 vascular, 3 tumoral cerebral lesions). Short-latency scalp somatosensory-evoked potentials (SEPs) to simultaneous median, and separate unilateral peroneal nerve stimulation were carried out before and after L-AC administration (at 10-, 30- and 60-min intervals). L-AC did not influence peak and interpeak latencies; however, in a percentage of healthy and diseased volunteers a clear-cut amplitude increase was evident affecting all those peaks generated between the thalamus and the cortex. While in normal and tumoral volunteers the voltage increase was bilaterally balanced, the amplitude increments were more evident on the 'affected' hemisphere in vascular patients, partially reversing the abnormal amplitude ratios between homologous peaks on 'healthy' and 'affected' hemispheres. In no case were transient clinical changes, either of an objective or subjective nature, associated with SEP amplitude changes; these were still present at the 60th minute, having reached their nadir at the 30th minute in 'responders'.

Brain-stem auditory evoked responses (BAERs) in patients with chronic renal failure.

Brain-stem auditory evoked responses have been investigated in 28 patients suffering from chronic renal failure (17 on diet, 11 on chronic dialysis) during monaural stimulation with 70 dB HL clicks. These responses were abnormal in 32.15% of cases. In 13 out of 15 years with altered BAERs a normal response morphology was present, with progressively more significant latency delays involving all peaks following wave I, while in the remaining two ears some of the components always found in healthy controls were not identifiable. The most prominent abnormality in patients with symptoms referable to peripheral neuropathy was the presence of a prolonged I-II interpeak latency, while in those without symptomatology the I-V and III-V interpeak times and the peak V latency were the most strikingly altered parameters. The incidence of altered BAERs was higher in the group of patients treated with diet than in the dialysed group. When BAERs were followed-up in the hours preceding and following the first dialysis in two patients not included in the previous group, the I-V interpeak time significantly decreased after 26 h from the end of dialysis.