F. Johansson

Tolerance and tremor rebound following long-term chronic thalamic stimulation for parkinsonian and essential tremor

Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson’s disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6–12 months after surgery. The mean voltage 1 week postoperatively was 1.45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up

Aim: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson’s disease (PD) at 6 years post surgery. Methods: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson’s Disease Rating Scale were used for evaluation. Results: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. Conclusion: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency: a case study.

We report a patient with advanced Parkinsons disease, including severe and frequent off periods with freezing of gait, moderate dysphonia, and some cognitive impairment, who underwent bilateral subthalamic nucleus (STN) stimulation. The patient was followed for 1 year after surgery, showing persistent good mobility without off periods and without freezing, which reverted completely when stopping the stimulation. There was deterioration of cognition as well as increased aphonia and drooling, all of which remained when the stimulation was turned off. The striking improvement in motor symptoms following STN stimulation was not paralleled by improvement in disability, probably as a result of a cognitive decline, suggesting a diagnosis of Parkinsons disease with dementia. We conclude that chronic STN stimulation is efficient in alleviating akinetic motor symptoms including gait freezing; this surgery should be offered before patients start to exhibit speech or cognitive disturbances.

Substance P in CSF of patients with chronic pain syndromes

&NA; Immunoreactive substance P was determined in lumbar CSF of 35 healthy volunteers and 60 patients with chronic pain syndromes of at least 6 months duration. No significant relationships were found between substance P levels and age, sex or body height. Substance P levels were lower in chronic pain patients, with either neurogenic (n = 23) or idiopathic pain (n = 37) syndromes, than in the healthy volunteers. Substance P levels were especially low in patients with neurogenic pain with lesions involving the extremities and in those with polyneuropathy, while patients with central pain or pain of the head or face had higher values. Substance P levels were related to depressive symptomatology as determined by means of visual analogue scales and to stable personality traits as determined by means of the Karolinska Scales of Personality (KSP). The most consistent (and inverse) relationship was found between substance P levels and the symptom ‘inner tension’ and between substance P levels and the personality trait ‘psychic anxiety.’

Personality traits in chronic pain patients related to endorphin levels in cerebrospinal fluid

Interindividual differences in endorphin levels may relate to widespread changes in adaptive processes, and endorphin levels may thus be related to personality traits. In 40 patients with chronic pain syndromes of both psychogenic and organic origin, endorphin levels in cerebrospinal fluid (CSF) were determined, and the patients completed Eysencks Personality Inventory (EPI) and the Cesarek Marke Personality Scheme. Twenty-seven of the patients also completed the Zuckerman Sensation Seeking Scale (SSS). As a comparison group 30 healthy volunteers completed the personality inventories. The chronic pain patients were characterized by guilt feelings, need for order, low need for autonomy, and low tendency toward sensation seeking. Low levels of endorphins in CSF were found in patients with high scores on all the subscales in the SSS and low scores on the neuroticism subscale in the EPI.

Changes in endorphins and 5-hydroxyindoleacetic acid in cerebrospinal fluid as a result of treatment with a serotonin reuptake inhibitor (zimelidine) in chronic pain patients

Both the endorphin and the serotonin systems seem to be involved in pain perception, and a significant positive correlation between the levels of endorphins and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) has been established. In the present study, 20 chronic pain patients were treated with zimelidine, a rather selective inhibitor of serotonin reuptake, or placebo. Zimelidine produced a significant pain relief and a significant reduction of the levels of endorphins and 5-HIAA in CSF, while no significant changes occurred during placebo treatment. The results indicate that both the endorphin and the serotonin systems are involved in pain perception and that the systems are functionally related.

Quantitative electromyography of the external anal sphincter in Parkinson's disease and multiple system atrophy

The distinction of multiple system atrophy (MSA) from Parkinson′s disease (PD) can be difficult, especially early in the disease. In MSA degeneration of sacral anterior horn cells (Onufs nucleus) results in denervation‐reinnervation of anal and urethral sphincter muscles, which can be recognized as neurogenic electromyographic (EMG) changes of motor unit potentials. Sphincter EMG has therefore been recommended as a test for distinguishing MSA from PD. Our results confirm the presence of marked neurogenic EMG changes of the external anal sphincter muscle in patients with probable MSA compared to healthy controls. However, in patients with probable PD, our quantitative EMG data show a scatter from normal to marked neurogenic changes and the degree of EMG abnormality is correlated to the duration of the disease. Thus an abnormal sphincter EMG cannot be taken as a strong indicator of MSA rather than PD in the individual patient, especially in long‐standing cases.

Relationship between platelet MAO activity and concentrations of 5-HIAA and HVA in cerebrospinal fluid in chronic pain patients

Platelet monoamine oxidase (MAO) activity and concentrations of 5-HIAA and HVA in the cerebrospinal fluid (CSF) were estimated in a series of 54 chronic pain patients. Platelet MAO activity was found to correlate, positively to CSF concentrations of 5-HIAA and HVA, which had been adjusted in order to eliminate the influence of age and body height. However, only the correlation with 5-HIAA reached a significant level. When partial correlations were sought, only the positive correlation between platelet MAO activity and CSF 5-HIAA remained. The results support the notion that platelet MAO ia a biological marker for some trait dependent property of the central serotonergic system.

Long-term high frequency transcutaneous electrical nerve stimulation (hi-TNS) in chronic pain. Clinical response and effects on CSF-endorphins, monoamine metabolites, substance P-like immunoreactivity (SPLI) and pain measures

Eighteen patients with chronic pain syndromes of organic origin were treated by means of high frequency transcutaneous nerve stimulation (hi-TNS). The CSF levels of receptorassayable Fraction I and II endorphins, substance P-like immunoreactivity (SPLI), and the monoamine metabolites 5-HIAA, HVA and MOPEG were measured before and after one week of daily treatment. Furthermore, the effects on experimental pain measures were determined. The therapeutic effect was evaluated after 30 days and 3 months of treatment. Patients with low initial concentrations of endorphins in CSF, lower than those observed in healthy volunteers, tended to have the best response to hi-TNS. There were significant increases in Fraction I endorphins and SPLI in CSF, most pronounced in the patients who responded. There were no significant changes in 5-HIAA, HVA or MOPEG in CSF. However, in early responders, the serotonin metabolite 5-HIAA tended to decrease as contrasted to an increase in non-responders. The difference between the groups was statistically significant. Confirming our earlier studies, the therapy induced changes in pain measures showed a significant, positive correlation with increasing Fraction I endorphins in CSF. Our results suggest that hi-TNS induces central changes in the endorphinergic, serotonergic and possibly substance-P-ergic systems.

Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study

Abstract– In a double‐blind, cross‐over multicentre trial, the prophylactic antimigraine effect of the beta1‐selective beta‐blocker metoprolol was evaluated and compared with that of the non‐selective beta‐blocker propranolol. Metoprolol was used in a dosage of 50 mg b.i.d. and propranolol in 40 mg b.i.d.