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Fourteen obese patients (body mass index = 34-47 kg/m2; mean = 40 kg/m2) with lumbar cerebrospinal fluid pressure (Pcsf) above 20 cm water in 10 of the 14 patients were treated with digoxin with a serum concentration of at least 1.0 nmol/L (0.8 ng/ml) for 6 months. Pcsf decreased significantly during digoxin medication (p < 0.005). Although there were no diet restrictions, all patients decreased in weight (range: 3-25 kg; mean = 10.6 kg) during the 6 months (p < 0.001). When digoxin medication was stopped in 3 patients, prompt weight increase occurred. Most patients needed progressively increased digoxin doses to attain stabilized serum concentrations at the stipulated level, in 5 patients more than 0.5 mg a day. Five of 13 patients developed diabetes mellitus during the digoxin medication. The larger the dose of digoxin, the greater the risk for diabetes mellitus to occur. [ABSTRACT FROM AUTHOR]

The recruitment order of motor units was studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies of normal subjects that the recruitment order in sustained voluntary contraction is predominantly stable, and that motor units which increase slowly in discharge rate with increasing contraction strength and which already attain regular discharge intervals at low frequencies are always recruited before motor units which increase more rapidly in discharge rate and which do not attain regular discharge intervals until at higher frequencies. In this study 15 patients with severe cerebellar ataxia were examined. It was shown that the recruitment order in sustained voluntary contraction in attaxia is unstable and that low- and high-frequency motor units may alternate as the unit of lowest threshold. [ABSTRACT FROM AUTHOR]

The recruitment of motor units is studied with an electromyographic technique for secure identification of single motor unit potentials. It has been shown in previous studies that the recruitment order is different in tonic and in phasic activities; in tonic activity the recruitment order is stable and low frequency units are always recruited before high frequency units; in phasic activity, however, the recruitment order is unstable and units with a higher frequency range may be recruited before units with lower frequency range. In this investigation the shifts between tonic and phasic recruitment order in voluntary contraction were compared in normal subjects and in patients with severe bradykinesia of Parkinsonism. Upon initiation of a voluntary contraction in a normal subject, phasic recruitment order may be used for a few 100 msec but tonic recruitment order then takes over. In bradykinetic patients, however, this shift from phasic to tonic recruitment order is delayed. After termination of tonic voluntary contraction in a normal subject, phasic recruitment order can again be used after a few seconds. In bradykinetic patients, however, the shift back from tonic to phasic recruitment order is also delayed. In favourable experimental situations the shift from phasic to tonic recruitment order can be normalized by passive stretch of the muscle and the shift from tonic to phasic recruitment pattern by unloading the muscle. It is discussed whether the pathological recruitment in bradykinesia might be due to disturbed gamma loop function. [ABSTRACT FROM AUTHOR]

The recruitment order of motor units in the tibialis anterior muscle upon fatigue of tonic voluntary contraction was studied in 20 patients with severe spastic paraparesis. An electromyographic technique for secure identification of single motor units was used. Before fatigue the recruitment order is stable and low-frequency units are recruited before high-frequency units; this recruitment pattern agrees with that in normal voluntary activity. When fatigue appears, however, the recruitment order becomes indefinite and high-frequency units can be recruited before low-frequency units; this recruitment pattern agrees with that in normal phasic voluntary activity. Finally, all voluntary activation power disappears, even in the case of units which have never been active. Contraction ability and original recruitment order are restored upon rest but also upon tonic reflex support of the voluntary drive. Whether the fatigue reaction may be due to insufficient gamma motoneurone innervation and whether it is related to spasticity are discussed. The practical physiotherapeutic implications are reviewed. [ABSTRACT FROM AUTHOR]

It has been shown in previous investigations that the recruitment order of motor units is different in tonic and in phasic voluntary activity. The significance of the pre-existing state of facilitation in the motoneurone pool for the recruitment of units is studied, using the phasic flexion reflex in the anterior tibial muscle as test reflex. It is shown that the recruitment order of units in a series of reflexes (1) is unstable if the subject does not expect the stimulus; (2) is stable and identical with that in tonic activity if the subject subliminally facilitates the motoneurone pool before the reflex activation; (3) is stable and almost identical with that in tonic activity if the subject expects the stimulus and therefore involuntarily influences the motoneurone pool; (4) is stable and similar to that in phasic voluntary activity if the subject inhibits the motoneurone pool before the activation and the stimulus strength thus consequentially is increased; and (5) is influenced by blockade of the proprioceptive afferent impulses from the muscle. It is concluded that normal man can select in advance the recruitment order of motor units most appropriate for the work intended. [ABSTRACT FROM AUTHOR]

The recruitment order of motoneurones in muscle contractions has been held to be largely constant and determined by the size of the cell. However, as shown in a previous investigation using electromyographic techniques, the order in which different motor units are activated during voluntary muscle contractions changes in normal human subjects on shifts from phasic to tonic contraction. In order to investigate these two types of activity also in cases in which the cerebral influence on the motoneurone pool is blocked, an analysis was made of the recruitment order in phasic and tonic flexion reflexes in 10 patients with total interruption of the spinal cord. The following four principles were found to apply and presumed to be generally valid for the isolated human spinal cord: (1) in the phasic exteroceptive reflex, the order of recruitment varies despite application of a standardized stimulus; (2) in the tonic reflex, the first unit to be recruited is usually the same even with widely different types of stimuli; (3) a shift from phasic to tonic reflex activation may result in considerable changes in recruitment order; (4) after facilitation by a subliminal long-lasting stimulus, the first unit to be recruited in the phasic reflex is also the first to be recruited in the tonic reflex. It is suggested that a tonic influence on the motoneurone pool is required for the presupposed constancy of the recruitment order. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor responding to comments made on the author's article about the craniovascular and hemodynamic responses to head-down tilt in patients felt to have a diagnosis of chronic tension type headache.

Background: Pathologic signs in orbital phlebographies have been reported in various neurological diseases., Purpose: To study if pathologic signs in orbital phlebography may be markers of inflammation primarily affecting intracranial capillaries, which would cause intracranial hypertension., Material and Methods: Two groups with different intracranial cerebrospinal fluid pressures (Pcsf) were compared as to inflammatory markers in serum and pathologic signs in orbital phlebographies. Nine consecutive patients with idiopathic intracranial hypertension (IIH) with bilateral papilledema and eight consecutive patients with chronic tension-type headache (CTTH) were investigated prospectively with fibrinogen, orosomucoid, haptoglobin in serum, and invasive orbital phlebograms. The angiograms were evaluated by two skilled neuroradiologists, independent of each other and without knowledge of the diagnoses or aim of the study, as to the following pathologic signs: (i) narrowing of superior ophthalmic veins; (ii) caliber changes of intraorbital veins; (iii) collaterals of intraorbital veins; (iv) flow to cavernous sinus; and (v) asymmetric drainage of cavernous sinus., Results: Mean body mass index was >30 kg/m(2) in both groups. Pcsf was >200 < 250 mm H2O in 50% of the CTTH and >350 mm H2O in all IIH patients. No difference in inflammatory markers in blood was found. The phlebographies of the IIH patients had more pathologic signs and were considered pathologic significantly more often than the ones of the CTTH patients (P < 0.001)., Conclusion: The difference as to phlebographic pathologic signs between the IIH and the CTTH patients with different Pcsf supports the hypothesis that such phlebographic signs are markers of inflammation primarily affecting intracranial capillaries, which would disturb cerebrospinal fluid regulation causing intracranial hypertension.

Objective: Idiopathic intracranial hypertension (IIH) is usually considered to result from deficient intracranial absorption of cerebrospinal fluid, but has also been suggested to be caused by decreased cranial venous flow because of increased intrathoracic pressure resulting from intra-abdominal obesity. To test this hypothesis, cerebrospinal fluid pressure (Pcsf), extracranial venous pressure (Pvf), intracranial venous pressure, and body mass index (BMI) were studied in patients with IIH with papilledema compared with patients with chronic tension-type headache (CTTH)., Design and Subjects: The Pcsf and the pressures in frontal veins without (Pvf) and with bilateral compression of the supraorbital branch of the frontal veins and the superficial facial veins (Pvfc), the latter considered to be about equal to Pvfc, were studied in 10 consecutive patients with IIH with papilledema. Ten consecutive CTTH patients were used for controls. Orbital phlebography was performed to confirm that the compression of facial veins other than the frontal veins resulted in adequate communication between the frontal vein used for the studies and the cavernous sinus., Results: Cerebrospinal fluid pressure was between 200 and 250 mm water in 5 of the CTTH patients and above 350 mm water in all IIH patients. Body mass index was >25 in all CTTH patients and similar in the 2 groups. Cerebrospinal fluid pressure was similar to Pvfc in all 10 CTTH patients but significantly greater in 6 of the 10 IIH patients. Pvf was similar in the 2 groups and related to BMI., Conclusions: Chronic tension-type headache patients may be prone to have Pcsf > 200 mm water and BMI > 25. Papilledema because of intracranial hypertension occurred in the present study at Pcsf > 350 mm water. The findings of Pvfc and Pcsf being similar in all CTTH patients support the suggestion that the techniques used for measuring intracranial venous pressure are adequate. The findings of similar BMI in the CTTH and the IIH patients who differed significantly as to Pcsf refute the hypothesis that obesity precedes, and is the cause of, intracranial hypertension in IIH. The difference between Pcsf and Pvfc in 6 of the IIH patients also does not support such a hypothesis but may indicate that IIH is due to deficient intracranial cerebrospinal fluid absorption. Since a relationship between intracranial hypertension and obesity is established and obesity is not found to cause intracranial hypertension in IIH, intracranial hypertension may be suggested to be the primary cause of weight increase in IIH. Obesity, however, may secondarily increase the preexistent IIH.

Methods: Twelve consecutive patients with clinical symptoms and testing results compatible with a diagnosis of idiopathic intracranial hypotension (IIH), but no identifiable site of cerebrospinal fluid (CSF) leakage, were treated with a cervicothoracic or lumbar epidural "blood patch" (EBP) or orally administered steroids., Results: Prompt and complete relief from headache persisting for at least 4 months was attained in 3 of 4 treatments with cervicothoracic EBP, 2 of 15 with lumbar EBP, and 4 of 8 with steroids., Conclusion: These results suggest that in patients who presumably suffer from IIH and yet have no identifiable site of CSF leakage, the presumed leakage more often occurs at the cervicothoracic level than the lumbar. In addition, our experience suggests that some IIH patients may be treated effectively with oral steroids and a trial of such therapy may be considered as an alternative to EBP.

After dissection with complete occlusion of the internal carotid artery, a 58-year-old man started to suffer from intense cluster headache-like attacks. Magnetic imaging showed signs of nonsymptomatic cerebral emboli, which could be dated to have occurred in temporal relation to the start of the attacks, all on the right side. This case and two similar ones indicate that peripheral postganglionic sympathicoplegia can cause attacks with similar pain characteristics, accompanying symptoms, duration, and regularity as in cluster headache.

T cell Ig- and mucin-domain-containing molecules (TIMs) comprise a recently described family of molecules expressed on T cells. TIM-3 has been shown to be expressed on murine Th1 cell clones and has been implicated in the pathogenesis of Th1-driven experimental autoimmune encephalomyelitis. In contrast, association of TIM-1 polymorphisms to Th2-related airway hyperreactivity has been suggested in mice. The TIM molecules have not been investigated in human Th1- or Th2-mediated diseases. Using real-time (TaqMan) RT-PCR, we show that human Th1 lines expressed higher TIM-3 mRNA levels, while Th2 lines demonstrated a higher expression of TIM-1. Analysis of cerebrospinal fluid mononuclear cells obtained from patients with multiple sclerosis revealed significantly higher mRNA expression of TIM-1 compared with controls. Moreover, higher TIM-1 expression was associated with clinical remissions and low expression of IFN-gamma mRNA in cerebrospinal fluid mononuclear cells. In contrast, expression of TIM-3 correlated well with high expression of IFN-gamma and TNF-alpha. These data imply the differential expression of human TIM molecules by Th1 and Th2 cells and may suggest their differential involvement in different phases of a human autoimmune disease.

Objective: To investigate the mechanisms behind the increase of chronic tension-type headache during head-down tilt., Background: The pathophysiology of chronic tension-type headache is unknown., Design and Methods: Ten patients suffering from chronic tension-type headache and 10 age- and sex-matched controls were studied with respect to pain intensity and alterations in cranial blood volume using planar scintigraphy and radiolabeled autologous erythrocytes before, during, and after head-down tilt, a procedure known to increase chronic tension-type headache., Results: Four of 8 patients with chronic tension-type headache studied had increased cerebrospinal fluid pressure. During head-down tilt, the pain increased significantly in the group with chronic tension-type headache (P <.001) while the procedure did not cause headache in the controls. Blood volume significantly increased extracranially and decreased intracranially in both groups during head-down tilt. The extracranial nasal blood volume was significantly related to the pain experienced by the patients with chronic tension-type headache before and during head-down tilt., Conclusions: Although the changes in blood volume and, presumably, the increase of intracranial pressure were similar in the patients with chronic tension-type headache and the controls, only the patients experienced pain and pain increase during head-down tilt. This indicates that the pre-head-down tilt conditions must be different in the 2 groups and should be related to increased cerebrospinal fluid pressure/intracranial venous pressure in patients with chronic tension-type headache compared with controls. A difference in central mechanisms may, however, also be of importance for the difference in headache provocation in the 2 groups during head-down tilt.

Objective: To study the relationship between chronic tension-type headache, cranial hemodynamics, and cerebrospinal pressure., Background: Cerebrospinal pressure has been found to be above 200 mm in about 50% of patients with chronic tension-type headache., Methods: Heart rate, blood pressure, common carotid artery diameter and blood flow, and craniovascular resistance and pain at regular intervals before, during, and after head-down tilt-a procedure which increases cerebrospinal pressure, were recorded. After head-down tilt, subcutaneous injections of either placebo or 6 mg of sumatriptan were administered. Chronic tension-type headache intensity before and after withdrawal of 20 mL of cerebrospinal fluid was documented. Cerebrospinal pressure and chronic tension-type headache intensity were measured after subcutaneous injection of 6 mg of sumatriptan., Results: Head-down tilt provoked an increase of headache compared with baseline. Common carotid artery blood flow decreased and craniovascular resistance increased after sumatriptan injection, but not after placebo injection. The pain decreased after head-down tilt and placebo injection, but not after sumatriptan injection. Chronic tension-type headache intensity decreased in all 4 patients studied after withdrawal of 20 mL of cerebrospinal fluid. Cerebrospinal pressure increased in 5 patients with chronic tension-type headache after subcutaneous injection of 6 mg of sumatriptan with slight or no increase of pain., Conclusion: The results indicated that cerebrospinal pressure or intracranial venous pressure (or both) are related to chronic tension-type headache.

Objective: To investigate similarities and differences between patients with cluster headache and patients with migraine., Background: Patients with migraine and patients with cluster headache are considered, by many clinical neurologists, to be different psychologically and socially., Methods: Twenty-five age-matched pairs of men and 24 age-matched pairs of women with either migraine or episodic cluster headache (men aged 31 to 62 years; mean, 47 years; women aged 23 to 72 years; mean, 44 years) were compared with regard to coping profiles as reflected in two "coping wheels," one for the present situation and one for the future. In addition, availability of attachment and social interaction was assessed by means of the ISSI (Interview Schedule for Social Interaction)., Results: Women with cluster headache anticipated fewer activities for themselves than women with migraine, and findings were similar in the male pairs. The men with cluster headache also anticipated significantly fewer activities for themselves in the present and with others in the present and in the future than the men with migraine. There was no significant difference as to emotional loading between the two groups. A tendency to more optimistic anticipation was found in the women with cluster headache. There were highly significant differences between the two groups in the "future" wheel. The group with migraine expected more concrete activities and more activities with their families in the future, and they also described their present situation to involve more activities with others., Conclusions: Results from the present study differ from those from studies utilizing more conventional questionnaires. In particular, we found that patients with cluster headache have fewer close social contacts than patients with migraine.

Three patients with bilateral chronic tension-type headache (meeting IHS diagnostic criteria) responded with complete control of the headache during the more than 2 years they were treated with indomethacin. The headache recurred within 12 to 26 hours after indomethacin was stopped. Fifty milligrams of intravenous indomethacin resulted in complete relief of headache for 6.5 to 25 hours, similar to results found earlier in patients with hemicrania continua. It is concluded that there may be a subgroup of patients with bilateral chronic headache who respond to indomethacin in the group of patients otherwise diagnosed as having chronic tension-type headache.

Twenty-seven patients with chronic tension-type headache were studied as to end-tidal PCO2, heart rate, mean blood pressure, diameter and blood flow of the common carotid arteries, cranial vascular resistance, and headache intensity at supine rest, after administration of nitroglycerin, and at head down tilt. The results were compared to the results of nitroglycerin and head down tilt provocations in age- and sex-matched controls. During supine rest, no change in chronic tension-type headache occurred. Nitroglycerin and tilting induced significant increase of the headache intensity compared to baseline in patients with chronic tension-type headache (P=0.01 and P<0.05, respectively) in contradistinction to controls who did not develop significant headache. Common carotid artery blood flow changes were similar during nitroglycerin provocations in the two groups, but greater (P<0.05) during head down tilt in patients than in controls. Lumbar cerebrospinal fluid pressure was found to be greater than 20 but less than 26 cm H2O in 45% of the 22 patients studied with chronic tension-type headache. The results indicate that the pain in chronic tension-type headache is related to cranial hemodynamics, presumably to distention of intracranial veins.