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-γ mRNA in cerebrospinal fluid mononuclear cells. In contrast, expression of TIM-3 correlated well with high expression of IFN-γ and TNF-α. 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.

1. The discharge properties of single motor units during prolonged maximal voluntary effort have been studied using electromyographic recordings, mainly in the short big toe extensor muscle but also in the anterior tibial muscle. 2. The required selectivity of the e.m.g. recordings was achieved in the short big toe extensor muscle after previous mechanical lesions to the terminal nerve twigs and muscle fibres and consequent collateral sprouting, and in the anterior tibial muscle with the use of a high impedance wire electrode. 3. During the first few hundred milliseconds of sustained maximal effort the motor units fired at rates ranging from about 30‐60 Hz, and the tension was the same as that obtained on electrical tetanization of the nerve to the toe extensor muscles above 50 Hz. 4. During prolonged maximal effort the firing rates and the proportion of motor units firing successively decreased. Motor units initially firing at 30 Hz continued to fire tonically but at 15‐20 Hz. Motor units initially firing at 60 Hz ceased to fire tonically but could still be made to discharge phasically. The period of time during which all motor units responded tonically could be increased from some seconds up to 20 sec by long‐term training. 5. Motor units with a limited endurance fired at a lower tension in the early than in the late stages of maintained contraction. 6. It is suggested that motoneurones innervating slow twitch muscle fibres respond continuously to prolonged voluntary drive at rates sufficient for full fusion but that the threshold of motoneurones innervating fast twitch muscle fibres increases so that they finally mainly fire phasically thus protecting the peripheral excitation and contractile mechanisms from excessive exhaustion.

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Recent functional brain imaging studies with positron emission tomography (PET) suggest a preference of the right hemisphere, especially the anterior cingulate cortex (ACC), in affective processing of the clinical pain syndromes. We have investigated the central processing of cluster headache (CH) attacks provoked by sublingual nitroglycerin (NTG). In the cerebrum, provoked CH activated the ACC and the temporopolar region of the right hemisphere in addition to other regions. The regions activated in the ACC (Brodmann area (BA) 24 and 32) are involved in affective/cognitive processing of pain and willed attention. Our study discloses the preferential role of the right hemisphere in attributing emotional valence and attention to the suffering of pain. The findings support the theory of a right hemispheric specialisation in the mediation of withdrawal-related negative affect. The divergence of the distributed central processing between provoked cluster headache attack and experimentally induced acute pain indicates different central mechanisms for different types of pain.

The discharge pattern and recruitment order of single motor units in voluntary contraction of the normal human anterior tibial muscle was studied with an electrode having a high selectivity and a high positional stability in the muscle. In sustained contractions each motor unit was activated at a characteristic level of tension. The higher the threshold of the motor unit in sustained contraction, the higher was the frequency when the unit attained a discharge at regular intervals and the higher tended the “maximum frequency‘‐of the unit to be. Motor units with low thresholds in sustained contractions exhibited a continuous or tonic discharge in strong sustained contractions, whereas units with high thresholds tended to exhibit a discontinuous or phasic discharge. For some units the threshold of activation remained stable, for others it increased during activity. In twitch contractions the recruitment order of motor units differed considerably from that in sustained contractions.

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.

One of our 7 patients (14%) with chronic cluster headache had an abnormal orbital phlebogram; this was significantly less than the 61% encountered in our 13 patients with active episodic cluster headache who had this test done. There were no pathologically increased values for serum haptoglobin or orosomucoid in our 9 patients with chronic cluster headache, again significantly less than in our 43 patients with active episodic cluster headache, 51 percent of whom had pathologically increased values of haptoglobin or orosomucoid. These inflammatory signs decreased after the episodic cluster headache was over. Episodic cluster headache we suggest to be due to temporary sympathicoplegia caused by venous vasculitis in the cavernous sinus region; chronic cluster headache we attribute to permanent post-inflammatory sympathicoplegia in the middle fossa.

Thirteen patients with cluster headache in an active stage were investigated with orbital phlebography. About 60% of the patients showed pathologic changes on the phlebograms, such as changes in the appearance of the superior ophthalmic vein. Five patients had pathologic changes on both sides and three patients on one side only. All patients with unilateral pathologic findings on orbital phlebography had the attacks on the same side. The phlebographic findings in these patients with cluster headache were very similar to those of patients with the Tolosa-Hunt syndrome. There is also some similarity in the symptoms in the two disorders. It has previously been suggested that the Tolosa-Hunt syndrome is caused by venous vasculitis, and the present findings to some extent support the idea that cluster headache may have the same etiology.