Effect of Vagal Nerve Electrostimulation on the Power Spectrum of Heart Rate Variability in Man

The power spectrum of heart rate variability contains low frequency (LF = 0.08-0.12 Hz) and high frequency (HF = 0.18-0.30 Hz) components said to represent neurocardiac rhythms. To verify whether such a relationship exists we report a unique study where the heart rate autospectrum was determined in a 28-year-old epileptic male patient with an implanted vagal electrical stimulator. The stimulator was activated at 20 Hz, 300 microseconds pulse, and 1.25 V. Continuous ECG and respiratory waveform records were obtained over 45 minutes every 8 hours (7-8 AM; 3-4 PM; 11-12 PM) with the stimulator ON, then 24 hours OFF and then 24 hours ON again. The overall LF:HF peak ratio increased from 0.64 to 1.99 (P less than 0.001) after the stimulator was turned OFF. There was a dramatic increase in the LF peak power (greater than 60%) and a corresponding decrease in the HF peak power (greater than 65%) when the stimulator was turned OFF. These values were reversed when the stimulator was turned ON again. In the early morning and late evening hours, there was a significant rightward shift in the LF peak power frequency (average 0.057 to 0.075 Hz) whenever the stimulator was ON. Otherwise, there were no significant circadian variations in any of the autospectral components. The results demonstrate an unequivocal relationship between selective vagal nerve electrostimulation and alterations in the heart rate autospectrum.     

Evaluation of an In-Line Bipolar Polyurethane Ventricular Pacing Lead

A study was undertaken to evaluate the performance of the Medtronic 4012 polyurethane in-line bipolar pacing electrode. One hundred twenty six patients implanted with the 4012 lead were followed by our clinic with 116 of these leads implanted at our institution. Patients were followed a minimum of every 4 months. Testing included the performance of stimulation thresholds, sensing thresholds, and provocative maneuvers to evaluate for myopotential inhibition testing a minimum of every eight months. There were 12 documented lead failures of the total 126 patients. Further analysis was limited to the ten failures occurring in the 116 leads implanted at our center. All ten failed leads utilized the suture anchoring sleeve. Six of the leads were left cephalic implants, three were right cephalic, and one was right subclavian. Manifestations of failure included: seven oversensing abnormalities, three undersensing, four loss of ventricular capture, one premature end of service, four lead impedance decreases to < 250 Ω and some presentations in combination. No leads were explanted for evaluation. The Kaplan-Meier product limit method was used to estimate the time to lead failure. The probability of not experiencing a lead failure within the first 4 years of implant is estimated to be 0.9103 (SE = 0.0338). Pacemaker dependent patients implanted with the 4012 lead should be given special consideration for prophylactic replacement.     

Clinical use of the Odstock dropped foot stimulator: its effect on the speed and effort of walking

OBJECTIVE: To assess the clinical effectiveness of the Odstock dropped foot stimulator by analysis of its effect on physiological cost index (PCI) and speed of walking. This functional electrical stimulation (FES) device stimulates the common peroneal nerve during the swing phase of gait. DESIGN: A retrospective study of patients who had used the device for 4 1/2 months. SUBJECTS: One hundred fifty-one patients with a dropped foot resulting from an upper motor neuron lesion. SETTING: A medical physics and biomedical engineering department of a district general hospital specializing in the clinical application of FES and a neurophysiotherapy department at a separate hospital. MAIN OUTCOME MEASURES: Changes in walking speed and effort of walking, as measured by PCI over a 10-meter course. RESULTS: There was a 92.7% compliance with treatment. Stroke patients showed a mean increase in walking speed of 27% (p<.01) and reduction in PCI of 31% (p<.01) with stimulation, and changes of 14% (p<.01) and 19% (p<.01), respectively, while not using the stimulator. Multiple sclerosis patients gained similar orthotic benefit but no "carry-over." CONCLUSIONS: The measured differences in walking with and without stimulation were statistically significant in the stroke and multiple sclerosis groups. In this study use of the stimulator improved walking. Those with stroke demonstrated a short-term "carry-over" effect.     

周围神经损伤的电刺激疗法

Wilson等人在动物实验中证实电刺激可促进周围神经再生。电刺激的种类有：全置入式、半置入式及非置入式。 Zanakis使用电场做了详细剂量研究,认为电流不是生理学上有关参数,而是电流密度即场强。电效应对神经再生的促进作用发生在最初几天,即生长的起始阶段,一旦神经再生开始、电场便对神经再生没有影响。电刺激促进神经再生机制目前尚不清楚,局部微环境建立特有渠道至靶细胞是非常重要的,包括多种生物电化学过程,与局部电的相互作用有关。     

T-lymphocyte immunophenotyping blind proficiency testing: a model system for CD4+ T-cells.

OBJECTIVE: To develop and evaluate methods and results for blind proficiency testing for CD4+ T-cells by T-lymphocyte immunophenotyping. DESIGN: A model system was developed to submit duplicate specimens for T-lymphocyte immunophenotyping as if they were routine patient specimens rather than proficiency specimens. Testing results were compared both interlaboratory and intralaboratory. The model system was designed to gather information on not just the analysis, but other segments of the total testing process. SETTING: Research facilities at the Graduate School of Public Health, San Diego State University, San Diego CA. PARTICIPANTS: 1) A healthy adult volunteer donating one pint of blood. 2) Laboratories offering T-lymphocyte immunophenotyping. MAIN OUTCOME MEASURES: 1) Feasibility of blind proficiency so that PT specimens are received, analyzed, and reported by laboratories without being identified as 'proficiency specimens.' 2) The ease and cost of such a system. 3) The comparability of results and report content among laboratories. RESULTS: A total of twenty-two laboratories received blind proficiency specimens. The model developed to submit specimens and receive results proved feasible. The interlaboratory coefficient of variation for CD4+ count for the four survey years ranged from 10% to 66% and for the CD4+ percent ranged from 4% to 15%. The per specimen cost in this blind proficiency testing was $437.65, approximately seven and a half times the cost for nonblinded proficiency testing or performance evaluations. CONCLUSIONS: Blind proficiency as a tool to compare laboratory test results for T-lymphocyte immunophenotyping is feasible but adds costs. The model system is useful to examine more of the laboratory total testing process than the analysis segment.     

Electrical Safety During Electrophysiological Testing

This report describes the inadvertent induction of non-sustained atrial and ventricular arrhythmias due to the malfunction of a programmable cardiac stimulator. The malfunction occurred when line power resumed after a brief municipal power outage ("blackout") during an invasive electrophysiological study. The stimulator spontaneously delivered very high frequency pulses through the electrode catheter to the myocardium which resulted in atrial and ventricular arrhythmias. During bench testing, the stimulator delivered a continuous train of high frequency output pulses (greater than or equal to 1 mA) when line voltage resumed normal level after it had dropped below 65 VAC. Electrical safety during electrophysiological testing requires a stimulator design which is immune to altered operating conditions, and which shuts down if abnormal operating or output conditions are detected.     

Combined Use of a True-Bipolar Sensing Implantable Cardioverter Defibrillator in a Patient Having a Prior Implantable Spinal Cord Stimulator for Intractable Pain

Reported is a case involving a patient with a previously implanted spinal cord stimulator (SCS) who presented for an implantable. Cardioverter defibrillator (ICD). The SCS device was located in the left lower abdominal quadrant with a stimulation electrode array placed on the dorsal aspect of the spinal cord at the T-11 thoracic level. Interaction testing demonstrated that the bipolar sensing transvenous ICD system (Medtronic 7221Cx PCD) did not detect the stimulator's output at burst rates ranging from 20–130 pulses/s, even with the ICD set to its maximum sensitivity of 0.15 mV and the stimulator programmed to the highest patient tolerated output combinations of 5 V, 0.45 ms in the bipolar configuration and 3 V, 0.45 ms in the unipolar (i.e., case-electrode) configuration.     

Comparative effectiveness of different stimulation modes in relieving pain. Part II. A double-blind controlled long-term clinical trial.

Part I of our earlier pilot study demonstrated that patients preferred modulated stimulation forms - frequency modulation and burst - rather than conventional continuous mode. To assess whether long-term therapeutic effects validate the immediate test results, this trial was performed in 14 patients with 21 pain conditions. Considering the results of the pilot study, the test stimulator was modified and 4 different forms of transcutaneous electrical nerve stimulation were randomly delivered to each patient who was blind to the modes of stimulation for 20 min. A second observer assessed the pain scores using visual analogue scales. The stimulation modes employed were: (1) conventional continuous stimulation (continuous pulses with a constant frequency of 70 Hz), (2) burst stimulation (80 msec long trains of pulses, each train consisting of 8 pulses, with an internal frequency of 90 Hz repeated 1.3 times a second), (3) high-rate frequency modulation, HRFM (continuous pulses changed from 90 Hz to 55 Hz over 90 msec, 1.3 times a second), (4) low-rate frequency modulation, LRFM (continuous pulses changed from 60 Hz to 20 Hz over 90 msec, 1.3 times a second). After the test treatment of 4 sessions in the clinic, depending on the pain scores and duration of pain relief recorded, the most effective stimulation mode was determined for each patient and a portable stimulator preset appropriately for that mode was given to be used at home, under our supervision, for 3 months. Fourteen pain conditions out of 21 (66%) responded well to the therapy; the majority preferred was the HRFM and burst-type stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safety and clinical efficacy of the double switch from originator infliximab to biosimilars CT‐P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicenter cohort study

Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT‐P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX‐double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single‐switched from originator IFX to CT‐P13 was performed, before and after an inverse probability of treatment weighting (IPTW)‐based propensity score analysis. Fifty‐two double‐switched patients with IBD were enrolled. The 24‐ and 52‐week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%–100%) and 90% (95% CI 81%–99%), respectively. Four patients experienced a total of five AEs, all graded 1–3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24‐week and follow‐up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double‐switch group with a single‐switch group of 66 patients with IBD; all these results were confirmed by IPTW‐adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT‐P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Biosimilars reduce the direct costs of therapy and facilitate access to high‐cost therapies to patients. Data show that switching from originator infliximab to infliximab biosimilars (CT‐P13 or SB2) is safe and effective. Few data are available on the outcomes of double switch (from biological originator to a first biosimilar and then to a second biosimilar), and caution has been expressed by the European Crohn’s and Colitis Organization (ECCO) and the Italian Group for the study of inflammatory bowel disease (IBD; IG‐IBD).

• WHAT QUESTION DID THIS STUDY ADDRESS?

The study was aimed to compare the effectiveness and safety of single and double switch of infliximab (IFX) in patients with IBDs.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

No differences were found in clinical response and remission as well as adverse events between either single or double IFX switch. Data were consistent with the safety profile of IFX.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Double switch strategy is safe and effective in IBD. These data assume high relevance in terms of cost‐savings strategies.     

A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease

To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.     

Electroencephalographic evoked pain response is suppressed by spinal cord stimulation in complex regional pain syndrome: a case report

Pain is a subjective response that limits assessment. The purpose of this case report was to explore how the objectivity of the electroencephalographic response to thermal stimuli would be affected by concurrent spinal cord stimulation. A patient had been implanted with a spinal cord stimulator for the management of complex regional pain syndrome of both hands for 8 years. Following ethical approval and written informed consent we induced thermal stimuli using the Medoc PATHWAY Pain & Sensory Evaluation System on the right hand of the patient with the spinal cord stimulator switched off and with the spinal cord stimulator switched on. The patient reported a clinically significant reduction in thermal induced pain using the numerical rating scale (71.4 % reduction) with spinal cord stimulator switched on. Analysis of electroencephalogram recordings indicated the occurrence of contact heat evoked potentials (N2–P2) with spinal cord stimulator off, but not with spinal cord stimulator on. This case report suggests that thermal pain can be reduced in complex regional pain syndrome patients with the use of spinal cord stimulation and offers objective validation of the reported outcomes with this treatment.     

Effects of Chronic Cerebellar Stimulation (CCS) Setting on the Gait and Speech of a Spastic Cerebral Palsy Adult

A single (N = 1) spastic cerebral palsy adult who had experienced Chronic Cerebellar Stimulation (CCS) for 9 years without any change in the stimulator settings was assessed at six different stimulator settings. These voltage settings varied from 0 volts to 40 volts and frequencies of stimulation from 0 to 200 Hz. Stimulation was with bipolar rectangular pulses with less than 0.2 C/mm2 charge per phase. Responses measured at each setting were quantitative gait, speech, and somatosensory evoked potential measurements. Additional clinical assessments were done by a neurologist and speech therapist. Alteration in stimulator settings occurred 1 week apart to allow for stabilization and all assessments were completed in the same sequence each day. None of the individual stimulator settings were known to any of the assessors or to the patient. The results showed consistently that the patient's gait and speech were poorest when the stimulator was switched off completely. Switching on the stimulator caused improved function according to all assessments. There was consistent improvement in gait and speech when the rate of the cerebellar stimuli was high (for voltages between 0 and 40 V). Changing the voltage (within the range 0 to 40 V), while keeping the frequency of stimulation constant, did not appear to have as much effect. This preliminary evaluation suggests that the technique of CCS is safe and can improve function in a measurable manner.     

Clinical follow-up after cessation of chronic electrical neuromodulation in patients with severe coronary artery disease: a prospective randomized controlled study on putative involvement of sympathetic activity

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.     

A prospective,multi-center randomized,controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment

Few treatment options exist for patients with difficult-to-treat depression (DTD). One potentially efficacious treatment is vagus nerve stimulation (VNS): chronic stimulation of the vagus nerve using an implanted stimulator. Given a series of recent VNS clinical studies, including a large, five-year naturalistic investigation, the Center for Medicare and Medicaid Services (CMS) reconsidered the previous non coverage determination and announced coverage for patients participating in a “coverage with evidence” trial. This study, entitled, A PRospective, Multi-cEnter, Randomized Controlled Blinded Trial DemOnstrating the Safety and Effectiveness of VNS Therapy® System as AdjunctivE Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER), includes DTD patients with at least four unsuccessful antidepressant treatments in the current episode and will randomize both unipolar and bipolar DTD participants, each up to 500 evaluable enrollees. Predetermined interim analyses will define the necessary sample size. All participants will be implanted with VNS devices: half receive active stimulation during year one, and half receive delayed stimulation after year one. Participants will be followed for 5 years. This RCT is unique for DTD studies: 1) large sample size and long study duration (one year of controlled comparison); 2) use of a percent time in response as the primary outcome measure, given the chronic illness and its fluctuating course (vis-à-vis meeting a response criteria at a single time point); 3) inclusion of diverse measures of VNS impact on function, including quality of life, degree of disability, health status, and suicidality.     

Feasibility of Long-Term Electrocardiographic Monitoring with an Implanted Device for Syncope Diagnosis

Patients with infrequent recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. The purpose of this pilot study was to assess the feasibility of using an implanted, long-term monitor as an aid to diagnosis in these patients. This was done using commercially available pacemakers with monitoring functions. Sixteen patients (eight males and eight femaiesj, aged 59.7 ± 17 years who had unexplained syncope despite a 12-lead electrocardiogram, repeated Holter monitoring, exercise testing, echocardiography, an eJectro-physioJogical study, and a tiJf test (n = 6), were entered into the study. Patients had experienced a mean of 3.3 ± 1 episodes of syncope in the 12 months prior to the study. All provided a history suggestive of Stokes-Adams attacks and were referred for consideration of pacemaker implantation. Two patients had ischemic heart disease and one patient had a long QT interval. Patients had an Intermedics Nova II or Medtronic Quintech DPG pulse generator capable of recording sensed and paced events implanted with a single right ventricular lead. Syncope or presyncope occurred in ten patients (62%) 4.9 ± 4.2 months after pacemaker implantation. Bradycardia was detected in six patients and four patients had no arrhythmia. In addition to bradycardia, one patient also had tachycardia detected. Pacing therapy resulted in symptom relief in all six patients with syncope or presyncope due to bradycardia. Complications of pacemaker implantation (lead insulation failure) occurred in two patients. One of these patients subsequently had an infection of the generator pocket with associated systemic sepsis. Although the devices used in this study have serious limitations, the results suggest that continuous long-term electrocardiographic monitoring can be useful in patients with recurrent syncope and a negative diagnostic work-up. A smaller device with self-contained electrodes designed for this purpose would be required for wider applicability.     

Practicality, safety and accuracy of computed tomography coronary angiography in the evaluation of low TIMI-risk score chest pain patients: a pilot study

Objectives: The present pilot study aimed to assess the practicality, safety and accuracy of performing CT coronary angiography (CT‐CA) in the evaluation of acute chest pain of patients with low thrombolysis in myocardial infarction (TIMI) risk scores. Methods: The present prospective observational study was undertaken in a university teaching hospital between November 2004 and December 2005. Participants were a convenience sample of patients admitted to hospital for investigation of chest pain with TIMI risk scores <3. Consenting patients underwent CT‐CA within 48 h of presentation. Outcomes of interest were practicality (proportion of diagnostic quality scans obtained and preparation time for CT‐CA), rate of serious adverse events, and accuracy at the patient level using selective coronary angiography as the reference standard. Results: Thirty‐four patients were recruited. Diagnostic quality scans were obtained in 26/34 or 76% of patients (four failed CT‐CA and four non‐diagnostic scans). The median CT preparation time was 1.9 h (range 0.17–4.0). No serious adverse events were found. Fourteen of those 26 patients with diagnostic CT‐CA subsequently had selective coronary angiography, of which nine were positive. The sensitivity and specificity of CT‐CA in identifying patients with significant coronary artery disease were 9/9 (100%; 95% confidence interval 72–100%) and 4/5 (80%; 95% confidence interval 28–100%), respectively. Conclusions: The majority of acute chest pain patients with low TIMI risk scores were successfully scanned with a 16‐slice CT to produce CT‐CA studies with good diagnostic quality and accuracy. No major adverse events were found. The place of CT‐CA in diagnostic workup for chest pain remains to be defined.     

Simultaneous thalamic deep brain stimulation and implantable cardioverter-defibrillator

Thalamic deep brain stimulation is becoming increasingly popular for the control of drug-refractory tremor. Implantable cardiac pacemakers and defibrillators are commonly used therapeutic modalities. Concerns exist about the potential interactions between these 2 devices in the same patient, but no experience has been reported previously. We describe a patient with essential tremor who had a deep brain stimulator implanted into the left ventral intermediate nucleus of thalamus, who subsequently needed an implantable cardioverter-defibrillator. Despite concerns about possible interactions between the 2 types of implanted electrical devices (i.e., a situation similar to drug-drug interactions), the deep brain stimulator and the implanted pacemaker-defibrillator functioned appropriately, and no interaction occurred in our patient.     

Nedocromil sodium in the management of chronic bronchial infection

A double–blind parallel group comparative pilot study was carried out in patients with bronchiectasis to evaluate the anti–inflammatory effect of nedocromil sodium in chronic bronchial infection. Patients were randomized to either a nedocromil sodium metered dose inhaler, 4 mg, four times daily, or placebo for 12 weeks. Clinical symptoms, lung function tests and sputum characteristics of volume, purulence, leucocyte count, neutrophil chemotactic activity and elastolytic activity were evaluated at baseline, after 4, 8 and 12 weeks of the trial. Patients were withdrawn when they had acute infective exacerbation. There were 13 evaluable patients and results were statistically analysed at 8 weeks due to the limited number of patients remaining in the study at 12 weeks. There was no significant change in any of the parameters in either active or placebo group. Hence, nedocromil sodium has not been found to contribute to the management of stable bronchiectasis in this study and larger studies are required to identify more modest effects.     

A New Advancement in Noninvasive Electrophysiology: A Standard Laboratory Stimulator Pulse Coupled with an Implanted Pacemaker

A new device for coupling the pulse from a standard laboratory stimulator to commercially available implanted pacemakers for use in noninvasive electrophysiology testing has been developed. When programmed to an electrophysiology mode, a 37 kHz carrier wave, generated by the programmer, maintains communication with the implanted pacemaker. Stimuli generated from a standard lab stimulator cause a break in the carrier wave and an output from the pacemaker. Cycle lengths as short as 127 msec can be attained. In addition to standard electrophysiology testing, this noninvasive electrophysiological technique can be used to fibrillate the heart to test the efficacy of automatic implantable cardioverter/defibrillators.     

Effectiveness and safety of using cyclosporin A in the treatment of primary Sj?gren's syndrome

We used oral cyclosporine-A (CyA) (5 mg/kg/day) initially in a double blind study for 6 mos. 10 patients received CyA and 10 placebo. At the end of this study it was observed that CyA improved subjective xerostomia, while subjective xerophthalmia, parotid gland enlargement, Schirmer-I-test and parotid flow rate did not show any significant differences in the two study groups. 9 of 10 patients who had received CyA for 6 mos and 9 of 10 in the placebo group continued in an open trial (CyA at the same dose) for an additional 6 mos. At the end of the study the only efficacy of CyA observed was improvement of subjective xerostomia. The side-effects observed were hypertrichosis (14 persons), mild hypertension (4), infections (5) and 3 dropped out because of nausea, tremor, paresthesias and infections. In conclusion, small doses of CyA for 12 mos are rather ineffective for Sjogren's syndrome.