Detection of anterior horn lesions by MRI in central European tick-borne encephalomyelitis

We report a case of central European tick-borne encephalitis with cervical myelitis presenting clinically as a lower motor neuron syndrome of the upper limbs with proximal asymmetrical pareses and atrophies. There were no sensory deficits nor signs of lesions of the spinal pathways or signs of encephalitis or meningitis. The affected motor fibers of the upper limbs were electrically inexcitable, but sensory findings were normal. Electromyography of the paralyzed muscles revealed pathological denervation activity without voluntary activation. The initial magnetic resonance imaging (MRI) showed a large hyperdense lesion in the anterior part of the cervical cord from C3 to T1. Despite the fact that MRI changes disappeared completely within 6 weeks the patient showed only little improvement in the paralyzed muscles after 6 months. To our knowledge, these MRI changes in patients with tick-borne encephalitis, consistent with an isolated anterior horn lesion, have never been reported previously. The course may have been aggravated by an initial antibiotic treatment with cephalosporins. Received: 4 May 1999 Received in revised form: 22 July 1999 Accepted: 26 July 1999     

Autoimmune maintenance and neuroprotection of the central nervous system

The genesis of immune privilege high in the evolutionary tree suggests that immune privilege is necessary, if not advantageous for the progressive development of the CNS. Upon reaching a certain degree of complexity, it seems as if the CNS was obliged to restrain the immune system from penetrating the blood-brain barrier. CNS autoimmunity against myelin proteins is known to be a contributory factor in the pathophysiology of multiple sclerosis and in the animal model of experimental autoimmune encephalomyelitis (EAE) (Wekerle, 1993). Such autoimmunity has therefore been regarded as detrimental and hence obviously undesirable. However, recent findings in our laboratory suggest that T-cell autoimmunity to CNS self-antigens (Moalem et al., 1999), if expressed at the right time and the right place, can do much good in the CNS. We shall review the experiments briefly, and then discuss their implications for our understanding of immune privilege and CNS maintenance after injury.     

Dendritic cells in experimental allergic encephalomyelitis and multiple sclerosis

The mechanisms by which autoimmune diseases are triggered and by which the activation of autoreactive T cells is initiated and maintained are not yet fully understood. As the most potent antigen presenting cells (APC), and also being responsible for antigen transport as well as primary sensitisation of T cells, dendritic cells (DC) are capable of breaking the state of self-ignorance and inducing aggressive autoreactive T cells. In the development of autoimmune diseases, different types of DC exhibit distinct properties for inducing Th1/Th2 cell responses. Appropriate cytokines can convert immunogenic DC to tolerogenic DC. Utilizing the possibility to promote the tolerogenic effects of DC, a new therapeutic tool might soon become available to treat multiple sclerosis and other autoimmune diseases.     

The axillary vein central venous catheter in severely burned patients

In severely burned patients the approach to the central vein is often difficult due to concomitant edema, but also due to the fact that the skin area, where commonly used approaches are performed, is burned as well, whereas the axillary region is often not involved. In order to perform an axillary approach to the central vein as an alternative to the commonly used approaches in patients, an anatomical dissection in fresh human cadavers was carried out. Considering the anatomical landmarks which were found during dissection of the axillary region, the axillary approach to the central vein was used in 35 patients in our intensive burn care unit with unaffected axillary skin. In three cases the only complication observed was an occasional puncture of the axillary artery without major hematoma. The infection rate of the catheters was similar to the commonly used puncture sites. This approach to the central venous line in severely burned patients can be recommended.     

Effects of local MAO inhibition in the locus coeruleus on extracellular serotonin and 5-HIAA during exposure to sensory and cardiovascular stimuli

Previously, we have shown that in the presence of pargyline the release of serotonin (5-HT) in the locus coeruleus is modulated by various sensory stimuli and blood pressure fluctuations. The aim of the present study was to investigate whether local inhibition of monoamine oxidase (MAO) influences basal and stimulus-induced release of 5-HT in the locus coeruleus. For this purpose, the locus coeruleus was superfused in the absence and in the presence of the MAO inhibitor pargyline. Additionally, we examined whether the release of the 5-HT metabolite 5-hydroxy-indole acetic acid (5-HIAA) in the locus coeruleus is altered in response to stimuli. The locus coeruleus of the conscious rat was superfused through a push-pull cannula with artificial cerebrospinal fluid (CSF). 5-HT and 5-HIAA were determined in the superfusate. The basal release rate of 5-HT and the basal outflow of 5-HIAA averaged 2.0 fmol/min and 69 fmol/min, respectively. The basal release rate of 5-HT and the 5-HIAA outflow were tetrodotoxin (TTX)-sensitive. In the absence of pargyline, the sensory stimuli noise stress or tail pinch, applied for 10 min, increased 5-HT and 5-HIAA outflow by 50–70%. In contrast, an experimentally induced rise in blood pressure for 10 min enhanced 5-HT release by 50%, but had no effect on 5-HIAA outflow. The release of 5-HT and/or 5-HIAA elicited by sensory stimuli or a blood pressure rise was abolished by TTX. Addition of pargyline to the CSF enhanced 5-HT release fourfold and slightly decreased 5-HIAA outflow. These levels remained stable throughout the entire observation period of 8 h. In the presence of pargyline, 5-HT release elicited by noise, tail pinch and increase in blood pressure was enhanced. It is concluded that superfusion with pargyline enhances 5-HT release and reduces 5-HIAA outflow in the locus coeruleus. Furthermore, the ability of sensory stimuli and baroreceptor activation to enhance 5-HT release is preserved during a prolonged pargyline-induced increase in extracellular 5-HT. Since sensory stimuli enhanced, while baroreceptor activation did not influence 5-HIAA outflow, 5-HIAA is not a reliable index for short-term changes in the activity of serotonergic neurons in the locus coeruleus. Received: 13 July 1998 / Accepted: 10 December 1998     

Alpha-motoneuron excitability at high altitude

Summary It has been hypothesized that chronic hypobaric hypoxia could lead to inhibition of the-motoneuron pool, thus limiting the maximal activation of working skeletal muscles. To test this hypothesis six subjects [32 (SEM 2) years] were evaluated in resting conditions, at sea level and after acclimatization at 5,050 m. The recruitment curves of the Hofmann-reflex (H-) and the direct muscle-response (M-) of the right soleus muscle were obtained by stimulating the posterior tibeal nerve with different intensities while recording the electromyogram of the soleus muscle. From the recorded data the net-motoneuron excitability (ratio of maximal H-reflex to M-response H_max : M_max ratio), the threshold and gain for both responses, obtained from linear regressions through the rising phase of the recruitment curves of both responses, as well as the latency times of both responses were determined. The latency times and the H_max :M_max ratio were unchanged at altitude. The thresholds of both responses and the gain of the M-response were unaltered. The gain of the H-response was significantly higher at altitude when compared to sea level. It is concluded that in the acclimatized subjects at rest the signal conduction velocity through the different parts of both pathways was unaltered and therefore nerve and muscle conduction velocity as well as synaptic and muscle end-plate transmission were unchanged, that the recruitment of the H-reflex was slightly facilitated after acclimatization to high altitude suggesting increased excitability of the-motoneurons, through either postsynaptic facilitatory changes in the soma or a different descending drive, and that the unchanged H_max:M_max ratio indicated no change in the net excitatory and inhibitory influences on the-motoneuron pool. The above hypothesis is thus not strengthened by the results that were, however, obtained in resting conditions.     

Type I familial amyloid polyneuropathy and pontine haemorrhage

A Portuguese female, aged 47 years, who had emigrated to Spain, was admitted to the hospital in 1991 for pontine haematoma. The patient, four siblings and her father were affected by a peripheral neuropathy, indicating autosomal dominant inheritance. The patient presented in the 2nd decade with sensory and motor neuropathy beginning in the lower extremities. Alternating constipation and diarrhoea, and urinary incontinence became uncontrollable. She had to be colostomised, and, eventually, confined to a wheelchair from the age of 43. Neurological examination showed bilateral facial involvement, and severe signs of sensory and motor peripheral neuropathy, and later right hemiplegia. There were abnormalities of atrial rhythm and left bundle branch block. Computerised axial tomography and magnetic resonance images demonstrated left-sided pontine haemorrhage. Nerve conduction studies revealed severe diminution of motor conduction velocity and absence or reduction of amplitude of sensory and motor action potentials. Inanition and a respiratory infection led to her death. Clinical diagnosis was type I familial amyloid polyneuropathy (FAP). Postmortem examination demonstrated amyloid deposits in peripheral nerves, including spinal roots and cranial nerves, leptomeninges, thyroid, breasts, heart, adrenal glands, kidneys, intestines, pancreas, and meningeal and some pontine vascular structures. Advanced pontine haematoma was verified. Cerebral haemorrhage usually occurs with cerebrovascular amyloidosis, but exceptionally with FAP. A minority of patients presenting with CNS haemorrhage showed arteriovenous malformation or embolism [Da Silva Horta and Dias Coelho (1960) Arch de Vecchi Anal Patol Med Clin 31=163–172]. However, amyloid deposition in some small pontine vessels could have played a role in the pathogenesis of haemorrhage in the present case.     

The influence of δ9-Tetrahydrocannabinol on intraocular pressure in the anaesthetized cat

⁹-Tetrahydrocannabinol (⁹-THC) was injected both intravenously and into the brain stem via the left vertebral artery. Contrary to results obtained with clonidine, neither the fall in intraocular pressure (IOP), nor the arterial hypotension induced by ⁹-THC, were enhanced after the central administration of the drug. For clonidine, a central mechanism underlying the ocular hypotensive effect has recently been proposed. This suggestion is based upon the enhanced fall in IOP after central administration of clonidine. The pontomedullary area is considered to be the main initial target of this drug. Obviously, the IOP-lavering mechanism of ⁹-THC is different from that of clonidine.     

Hexachlorophene and the central nervous system

Summary A study on hexachlorophene encephalopathy in mice and baboons is reported. By light microscopy, a severe spongiform lesion of the central nervous system (CNS) was localized in the white matter, without myelin breakdown or cellular reaction. By electron microscopy, the myelin alteration was characterized by wide intralamellar spaces or splitting developed in the intraperiod line of compact sheaths. The acute changes described were induced by administration of the drug by the digestive or cutancous routes at various dosage levels in an aqueous solution or in talcum powder. The toxic effects depended on the age of the animals, the survival times and the concentrations of hexachlorophene, i.e., 6%, 3%, and 0.5%. The findings are compared with previous reports on the neurotoxicity of hexachlorophene and other chemicals in humans and experimental animals. Hexachlorophene cannot be recommended for use in young infants because of its neurotoxicity in very low doses as demonstrated in the present report.     

Central effects of paraoxon on haemodynamics in the cat

Summary Application of paraoxon into the left vertebral artery (8–80 g) or both the left and right vertebral artery (4–8 g) of the anaesthetized cat evoked dose-dependent depressor effects, whereas heart rate was not influenced significantly. Also after systemic administration of paraoxon (150–825 g·kg^–1), while peripheral muscarinic receptors were blocked, depressor effects were still observed. Dose-response curves for the depressor response to paraoxon were established. Infusion of low doses of dexetimide via the vertebral artery prevented the hypotensive action of paraoxon. The distribution of this antimuscarinic drug in the brain was investigated. The depressor effect of paraoxon can be attributed to both a decrease in peripheral resistance and cardiac output. Decerebration and midcollicular transection were carried out in order to elucidate the site and mechanism of action. The depressor effect of paraoxon seems to be mediated by a central mechanism of action located within the lower brain stem.It is concluded that stimulation of muscarinic receptors in the pontomedullary region gives rise to the observed changes in haemodynamic parameters. Muscarinic receptors in the hypothalamus seem to be of minor importance for the hypotensive action of paraoxon.