Long-term treatment with methylphenidate for fatigue after traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) may cause long-lasting post-concussive symptoms, such as mental fatigue and concentration difficulties, and this may become the main hindrance for returning to work and studies. There is currently no effective treatment for long-lasting mental fatigue. In this hypothesis generating study, the long-term effects of methylphenidate on mental fatigue, cognitive function, and safety were assessed. MATERIALS & METHODS: Thirty participants who suffered from long-term post-concussion symptoms after a mild TBI or moderate TBI and who had reported positive effects with methylphenidate during an initial phase of this follow-up study were treated with methylphenidate for a further six months. RESULTS: After six-month follow-up, effects on Mental Fatigue Scale (MFS), depression, anxiety, and cognitive function (processing speed, attention, working memory) were significantly improved compared to baseline data (P < 0.001, respectively). Heart rate was significantly increased (P = 0.01), while blood pressure was not changed. CONCLUSIONS: Individuals suffering from prolonged symptoms after TBI reported reduced mental fatigue and improved cognitive functions with long-term methylphenidate treatment. It is suggested that methylphenidate can be a treatment option for long-term mental fatigue and cognitive impairment after a TBI, but further randomized control research is warranted.

Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury.

OBJECTIVE: Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury. METHODS: Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments. RESULTS: Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate. CONCLUSIONS: Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.

Evaluation of dosage, safety and effects of methylphenidate on post-traumatic brain injury symptoms with a focus on mental fatigue and pain.

OBJECTIVE: The neurobehavioural symptoms and pain following traumatic brain injury (TBI) can be long-lasting. The condition impairs the persons' ability to function in their work, studies and gatherings with family and friends. The aim of this study was to investigate dosage, safety and effects of methylphenidate on mental fatigue and pain. METHODS: Twenty-nine physically-well rehabilitated TBI victims, 28 with a mild TBI and one with TBI and also with pain in the neck, shoulders and head were included in the study. Methylphenidate was tested in each patient using three treatment strategies: no medication, low dose (5 mg × 3) and normal dose (20 mg × 3) for 4 weeks using a randomized cross-over design. RESULTS: Twenty-four patients completed the three treatment periods. Five participants discontinued, four females due to adverse reactions and one male due to attenuated motivation. Only minor adverse events were reported. Methylphenidate significantly decreased mental fatigue, as evaluated by the Mental Fatigue Scale (p < 0.001), and the effects on mental fatigue were dose-dependent. No effect on pain was detected. CONCLUSIONS: Methylphenidate decreased mental fatigue for subjects suffering a traumatic brain injury, the treatment is considered to be safe and is recommended, starting with a low dose.

Relations between experimentally induced tooth pain threshold changes, psychometrics and clinical pain relief following TENS. A retrospective study in patients with long-lasting pain.

The present study investigates the relationships between clinical pain relief, physiological and psychological parameters. Out of 50 patients with long-lasting musculoskeletal neck- and shoulder-pain treated with transcutaneous electrical nerve stimulation (TENS), 21 were selected and classified as responders (n = 13) or non-responders (n = 8). Tooth pain thresholds (PT) were measured before and after an experimental TENS treatment and the relative change in PT following the stimulation was calculated. Three psychometric self-inventories were administered: Zung Depression Scale, Spielberger's Trait Anxiety Scale and the Multidimensional Health Locus of Control Scale. Responders (R) and non-responders (NR) differed significantly from each other in the PT measurements as well as on the psychometric scales. NR exhibited higher levels of anxiety and depression, a more pronounced powerful other orientation and no change or a decrease in PT following TENS compared to R. These findings indicate relationships and interactions between physiological and psychological factors in patients with long-lasting pain.

Esophageal dysfunction in syndrome X.

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing or myocardial scintigraphy, but with angiographically "normal" coronary arteries. The etiology of this enticing syndrome is still not known. Besides myocardial ischemia, esophageal dysfunction and visceral hypersensitivity may play a role in the development of pain. The purpose of this study was to study esophageal function and visceral sensitivity in patients with syndrome X. Twenty consecutive patients with the diagnosis of syndrome X were investigated with esophageal manometry and a 24-hour pH recording. Visceral esophageal sensitivity was explored by balloon distention of the distal esophagus, as well as by instillation of acid. Twelve patients (67% of the 18 evaluated) had some abnormality on 24-hour pH monitoring; 2 had abnormal global acid exposure time (pH <4) and 7 had symptoms coincidental with episodes of pH <4. Seven patients (35%) had esophageal dysmotility including 5 with the "nutcracker" esophagus. Esophageal hypersensitivity to acid (n = 9) or distention (n = 13) was seen in 14 of the 20 patients. Eleven patients received acid suppressive therapy that resulted in amelioration of chest pain in 8 (73%). Thus, results suggest that esophageal hypersensitivity rather than gross functional abnormality is an important factor for the development of chest pain in patients with syndrome X, and that acid in the context of a hypersensitive esophagus is the main culprit. Acid suppression may ameliorate pain in a substantial proportion of patients.

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography.

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 +/- 4) to exercise (47 +/- 13 clearance units; p less than 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 +/- 6) to exercise (33 less than or equal to 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 +/- 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 +/- 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Nutcracker oesophagus: a double-blind, placebo-controlled, cross-over study of the effects of lansoprazole.

BACKGROUND: Nutcracker oesophagus is characterized by high-amplitude oesophageal contractions. Recent data have shown a high prevalence of gastro-oesophageal acid reflux in patients with nutcracker oesophagus and, in open-label trials, patients seemed to benefit from acid suppression. Therefore, it has been suggested that non-cardiac chest pain in patients with nutcracker oesophagus may be related to reflux rather than to the motor abnormality itself. AIMS: To investigate the effect of intensive acid-suppressive treatment on chest pain in patients with nutcracker oesophagus. METHODS: Nineteen patients with nutcracker oesophagus received lansoprazole or placebo in a double-blind, randomized, cross-over study. RESULTS: Significant reductions in pain intensity (P < 0.006) and pain duration (P < 0.05) were registered during the study. The magnitude of symptom relief achieved with lansoprazole did not differ significantly from that achieved with placebo. The motility pattern did not change during the study. CONCLUSIONS: This study does not prove that acid-suppressive therapy is effective for pain relief in nutcracker oesophagus. As the amelioration of pain was not accompanied by any change in the nutcracker oesophagus pattern, it is unlikely that the high-amplitude oesophageal contractions are the cause of pain. Thus, the possible role of acid in the pathophysiology of pain in nutcracker oesophagus needs further study.

Clinical outcome of patients treated with spinal cord stimulation for therapeutically refractory angina pectoris. The Working Group on Neurocardiology.

OBJECTIVE: To determine morbidity and mortality characteristics in patients treated with electrical neuromodulation for refractory angina pectoris. DESIGN: A retrospective multicentre study of patients treated with spinal cord stimulation between 1987 and 1997; 21 centres were contacted and 14 responded. SETTING: Specialist centres worldwide. PATIENTS: Questionnaires were returned on 517 patients, of whom 71% were male. One was lost to follow up. Mean (SD) age was 63.9 (10.1) years. Duration of angina pectoris was 8.1 (6.3) years. RESULTS: Before spinal cord stimulation, 66% of the patients had experienced myocardial infarction, 68% had three vessel disease, and in 24% the left ventricular ejection fraction (LVEF) was /= 71 years were independent predictors of mortality. During spinal cord stimulation, New York Heart Association functional class improved from 3.5 to 2.1 (p < 0.01); 25 of the deceased patients (24%) and 32 survivors (8%) experienced myocardial infarction; hospital admissions were significantly (p < 0.001) more common in the deceased group (66% v 37%). CONCLUSIONS: The clinical outcome of patients with intractable angina is not adversely affected by the chronic use of neurostimulation.

The effect of transcutaneous electric nerve stimulation in patients with therapy-resistant hypertension.

OBJECTIVES: Afferent nerve stimulation, such as acupuncture and transcutaneous electric nerve stimulation (TENS), has shown a blood pressure reduction in both animal and man. In the present open and non-controlled study we investigated the effect on 24-h ambulatory blood pressure of low frequency TENS in a group of hypertensive subjects who do not respond properly to pharmacological treatment. METHOD: Twelve patients were investigated. The patients were treated with TENS at two acupoints on both forearms for 30 min twice daily during 4 weeks. 24-hour ambulatory blood pressure monitoring was recorded 1 week before, at start, at the end and finally 1 week after the TENS treatment. RESULTS: The blood pressure did not change significantly during the run-in period. After 4 weeks of TENS, the mean systolic blood pressure decreased by 6.3 mm Hg (P < 0.05) and the mean diastolic blood pressure decreased by 3.7 mm Hg (P < 0.05). The blood pressure reduction remained unchanged 1 week after treatment. There was no change in mean heart rate. CONCLUSION: The present study suggests that continuous TENS may have additional blood pressure-lowering properties in hypertensive patients who do not respond properly to pharmacological treatment. The effect of TENS may also have a prolonged effect. Journal of Human Hypertension (2000) 14, 795-798

Safety aspects of spinal cord stimulation in severe angina pectoris.

BACKGROUND: Spinal cord stimulation has been used over the past decade for the treatment of patients suffering from intractable angina pectoris, despite having received optimal medical therapy, and who are unsuitable for further surgical intervention. The clinical results are promising and several studies have shown that the antianginal effect of the treatment is associated with a reduction in myocardial ischemia. It has been suggested, however, that spinal cord stimulation may only attenuate the transmission of pain from the heart, without influencing myocardial ischemia. This is a major safety concern when applying this treatment strategy. METHODS: The aim of this study was to assess the potentially unfavourable aspects of spinal cord stimulation in patients with severe coronary artery disease and angina pectoris by means of repeated long-term ECG recordings. Nineteen patients who had been accepted for implantation of spinal cord stimulators for the treatment of severe angina pectoris were included. RESULTS: No increases were noted in the frequency of ischemic episodes, the total ischemic burden, or the number of arrhythmic episodes during treatment. CONCLUSION: The results of this study do not indicate any unfavourable effects of spinal cord stimulation in severe angina pectoris in terms of an increase in the frequency or severity of myocardial ischemia during treatment with spinal cord stimulation.

Transcutaneous electrical nerve stimulation in unstable angina pectoris.

BACKGROUND: Silent ischemia is a strong predictor of unfavorable outcome in unstable angina pectoris. Dynamic continuous vector cardiography provides online detection of ischemic episodes. Transcutaneous electrical nerve stimulation (TENS) has been reported to have antianginal effects in patients with severe coronary artery disease and this is associated with a reduction in myocardial ischemia. The aim of the present study was to investigate the applicability of TENS in patients with unstable angina in the coronary care unit and the effects on vector cardiographic and biochemical markers of ischemia. METHODS: Thirty patients (14 in the TENS group and 16 in a placebo group) were included in a single-blind, placebo-controlled study after being admitted to the coronary care unit. Continuous vector cardiography, leakage of cardiac enzymes and consumption of analgesics were recorded for 24 h. RESULTS: TENS was well tolerated and did not interfere with standard treatment, although vectorcardiographic recording during actual stimulation was disturbed. There was a reduction in the number of silent ischemic ST change vector magnitude episodes (P = 0.02) and their duration (P = 0.01) in the TENS-treated group, and a nonsignificant reduction in the total number of ST change vector magnitude (painful plus silent) episodes (P = 0.09) and their duration (P = 0.05) and in leakage of cardiac enzymes (P = 0.12). There were no detectable differences in terms of episodes of pain leading to stimulation or consumption of analgesics. CONCLUSIONS: TENS seems to be a safe additional treatment in unstable angina pectoris and may reduce the number of ischemic events, by mechanisms apparently unrelated to the reduction of pain.

Spinal cord stimulation in angina pectoris with normal coronary arteriograms.

BACKGROUND: Patients with angina pectoris with normal coronary arteriograms, also known as Syndrome X (typical exercise-induced angina pectoris, positive exercise testing, and normal coronary arteriograms), are often difficult to treat with conventional forms of medical therapy. Spinal cord stimulation has been used in recent years for the treatment of severe angina pectoris refractory to conventional medical and surgical therapy in coronary artery disease. The aim of this study was to investigate the effects of spinal cord stimulation on angina pectoris with normal coronary arteriograms. METHODS: Twelve patients underwent five bicycle exercise tests, three tests without (control), and two tests with spinal cord stimulation treatment. RESULTS: The exercise tolerance of the patients increased (108 +/- 22 W versus 96 +/- 21 W; P < 0.001), the magnitude of ST-segment depression at comparable work load decreased (1.0 +/- 0.6 mm versus 1.5 +/- 0.9 mm; P < 0.01), time to angina increased (5.4 +/- 2.2 min versus 2.7 +/- 1.9 min; P < 0.01), and time to the appearance of ST-segment depression increased (3.5 +/- 1.9 min versus 2.4 +/- 1.6 min; P < 0.01). The rate-pressure product at maximum work load during treatment increased, compared with the maximum work load during the control session (28,038 +/- 6124 mmHg x bpm versus 25,222 +/- 4519 mmHg x bpm; P < 0.05) and the comparable work load during treatment (28,038 +/- th 6124 mmHg x bpm versus 24,795 +/- 5022 mmHg x bpm; P < 0.01). CONCLUSIONS: Spinal cord stimulation has beneficial effects in angina pectoris with normal coronary arteriograms in terms of relief of symptoms of angina pectoris and improvement of exercise tolerance. These effects may be associated with a reduction in myocardial ischemia.

Effects of spinal cord stimulation on coronary blood flow velocity.

BACKGROUND: Spinal cord stimulation (SCS) has been used in the treatment of severe angina pectoris since the 1980s. Several studies have shown both an antianginal and an anti-ischaemic effect. There are several theories about the mechanism behind the anti-ischaemic effect of SCS, including the possibility that it is dependent on an increase in coronary flow velocity. OBJECTIVE: To determine if there were effects of SCS on coronary flow velocity during cardiac stress. METHOD: Eight patients with severe anginal pain secondary to coronary artery disease who had been implanted with an SCS device were included in the study. In addition, four patients with syndrome X were examined. If possible, a Doppler guidewire was placed in the vessel corresponding to the ischaemic area revealed on a prior myocardial scintigram. A temporary pacemaker electrode was placed in the right atrium. Atrial pacing started at 80 beats/min and increased by 10 beats/min every 2 min until the patient experienced moderate angina; the pacing frequency was then maintained at the same level. After 2 min of pacing at this frequency, SCS treatment commenced; after a further 5 min, pacing was stopped. Throughout the procedure, coronary flow velocity, assessed as average peak velocity (APV), was monitored continually. RESULTS: APV increased during pacing in all the patients with coronary artery disease (mean increase 53%; P < 0.02). There were no significant changes in APV during maximum pacing frequency when stimulation was introduced. CONCLUSIONS: The results of this study do not support the theory that the anti-ischaemic effect of SCS is dependent on an increase in coronary flow velocity.

Spinal cord stimulation in cardiovascular disease.

Spinal cord stimulation in ischemic pain conditions has proved to be an effective method of treatment for many patients. The indications are ischemic pain in the extremities from peripheral vascular disease and angina pectoris. The long-term results show that the response rate for ischemic pain is 70% to 90%, while the corresponding results for neuropathic pain average approximately 50% to 70%, which actually makes ischemic pain a very good indication for SCS. SCS system implantation is a safe and quick operation performed under local anesthesia and well tolerated by the patient. A total implant of the lead and the pulse-generator in one stage seldom takes more than 1 hour. High sterility and prophylactic antibiotics are prerequisites to avoid postoperative problems. In atherosclerosis, SCS should be regarded as a method supplementary to vascular surgery, to be used for symptom recurrence after treatment or when there are technical obstacles to reconstructive surgery. SCS has proven to be extremely effective for the relief of ischemic rest pain, which constitutes the most severe problem for these patients. Today it is estimated that more than 7000 implants for PVD have been done in Europe. In a prospective randomized study, Jivegård et al have shown that SCS is a limb-saving treatment. For angina pectoris, SCS by now has become a routine supplementary method to conventional medical and surgical treatment. The technique is clinically effective, and several studies have shown decreased myocardial ischemia and decreased anginal pain during treatment. It is probable that the use of SCS in refractory angina will increase considerably in the 1990s.

Changes in arterial levels and myocardial metabolism of catecholamines during pacing-induced angina pectoris.

In order to elucidate the effects of atrial pacing on cardiac catecholamine metabolism, 11 patients were studied during cardiac catheterization. Blood samples were drawn from a peripheral artery and the coronary sinus for estimation of catecholamine concentrations. Heart rate was increased by 10 beats/min each minute, and all patients experienced chest pain at maximal pacing rate. Coronary sinus blood flow rose from 122 +/- 19 at rest to 208 +/- 25 ml/min at final pacing rate, and myocardial lactate extraction ratio decreased. There was no significant change in arterial epinephrine levels, whereas the extraction ratio decreased (p less than 0.05). The norepinephrine arterial levels increased at the final pacing rate (p less than 0.01). The calculated myocardial release increased as well, but not to a statistically significant degree. The exact mechanisms of the rise in sympathetic activity and arterial norepinephrine levels cannot be ascertained with the present study design. Myocardial ischemia with subsequent chest pain seems to be a probably cause for the increased sympathetic outflow.

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

OBJECTIVE: To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN: The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING: Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS: Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS: Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS: Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal.

[Treatment guidelines for refractory angina pectoris now available. Therapeutic methods varying between behavior therapy and heart transplantation]. / Nu finns riktlinjer för behandling av refraktär angina pectoris. Terapimetoderna har varierat från beteendeterapi till hjärttransplantation.

Refractory angina pectoris is defined as severe angina despite optimal medical and surgical/invasive treatment (CABG, PTCA). The epidemiology of this condition is unknown. The estimated yearly incidence is 2,000 patients in Sweden and 30,000-50,000 patients in Europe. The patient group is growing as a result of improved therapy. A number of additional treatment modalities have been developed during the last decades. The article summarises the scientifically and clinical basis of these treatments and gives recommendations concerning their use.

[Relief of pain by exercise! Increased physical activity can be a part of the therapeutic program in both acute and chronic pain]. / Mindre ont med motion! Okad fysisk aktivitet kan vara en del av behandlingsprogrammet vid såväl akut som kronisk smärta.

Physical activity can relieve acute as well as chronic pain and has therefore an important role in the treatment of pain, directly or indirectly (by reducing anxiety and lifting depression). Physical inactivity is associated with higher morbidity/mortality and is as detrimental to people with chronic pain as it is to others. When including physical activity in pain treatment programmes it is important to tailor the exercise to suit the individual patient.

[Spinal cord stimulation in severe angina pectoris. Reduced ischemia and increased quality of life]. / Ryggmärgsstimulering vid svår angina pectoris. Minskad ischemi och ökad livskvalitet.

Promising clinical results have been obtained with spinal cord stimulation which in recent years has been used for treating the subgroup of patients with angina pectoris that has proved intractable to conventional medical and surgical treatment strategies. According to recent reports, the anti-angina effect of spinal cord stimulation is associated with a reduction in myocardial ischaemia due to decreased myocardial oxygen consumption. Candidates for the treatment require careful screening. It is important to ensure that the patient is capable of full co-operation, and that the chest pain is due to true reversible myocardial ischaemia. Results in the 206 patients given implants to date have been encouraging, with reductions both in the frequency of angina attacks and in the consumption of short-acting nitroglycerin.

[A patient with aortic dissection and abdominal aortic aneurysm with fistula]. / Patient hade både aortadissektion och bukaortaaneurysm med fistel.

Aneurysm of the abdominal aorta is not uncommon in later life. The frequency of aneurysm rupture varies with aneurysm diameter. In rare cases, the aneurysm may rupture intra-abdominally into surrounding structures and give rise to a fistula. When blood vessels are involved, the commonest form is aortocaval fistula, the presenting symptoms being those of severe right-ventricular heart failure. Although thoracic aorta dissection may be made manifest in acute intense chest pain, it is asymptomatic in up to 50 per cent of cases. The article consists in a case report of asymptomatic thoracic aorta dissection occurring concomitantly with a ruptured abdominal aneurysm the symptoms of which were severe right ventricular heart failure due to an aortocaval fistula causing increased pressure, and severe bilateral oedema of the legs. If the rare complication of an aortocaval fistula could be detected earlier, it might be possible to prevent progression to refractory cardiac failure. The possibility of a fistula should be borne in mind if haematuria is present in a case of abdominal aneurysm or a pulsatile abdominal mass is present in conjunction with a murmur.