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The majority of disease-modifying drugs (DMDs) available for the management of active relapsing-remitting multiple sclerosis (RMS) depend on continuous drug intake for maintained efficacy, with escalation to a more active drug when an unacceptable level of disease activity returns. Among continuously applied regimens, interferons and glatiramer acetate act as immunomodulators, while dimethyl fumarate, fingolimod, ocrelizumab, natalizumab and teriflunomide are associated with continuous immunosuppression. By contrast, immune reconstitution therapy (IRT) provides efficacy that outlasts a short course of treatment. Autologous hemopoietic stem cell transplantation is perhaps the classic example of IRT, but this invasive and intensive therapy has challenging side-effects. A short treatment course of a pharmacologic agent hypothesized to act as an IRT, such as Cladribine Tablets 3.5 mg/kg or alemtuzumab, can provide long-term suppression of MS disease activity, without need for continuous treatment (the anti-CD20 mechanism of ocrelizumab has the potential to act as an IRT, but is administered continuously, at 6-monthly intervals). Cladribine Tablets 3.5 mg/kg shows some selectivity in targeting adaptive immunity with a lesser effect on innate immunity. The introduction of IRT-like disease-modifying drugs (DMDs) challenges the traditional maintenance/escalation mode of treatment and raises new questions about how disease activity is measured. In this review, we consider a modern classification of DMDs for MS and its implications for the care of patients in the IRT era.

Plain radiography, myelography and post-myelographic CT-scan are described and related to clinical findings in a prospective study of 153 consecutive patients with myelographic signs of spinal cord compression. The majority of the metastatic tumours arise in the vertebral body or the pedicles. In 80% of the patients with total blockage to the contrast medium on myelography the post-myelographic-CT showed passage of the contrast medium. Ambulatory function at time of diagnosis was correlated to the degree and the localization of the epidural block. In 64 patients who underwent a second myelography, the post-treatment findings of sensory function were correlated to radiological regression.

Comparison between myelography (MY) and magnetic resonance imaging (MRI) was carried out in 36 patients with clinical suspicion of spinal cord or root compression due to metastatic disease in the spinal canal. In 3 patients metastatic lesions were visualized on MY but not on MRI, while there were no cases with a negative MY and a positive MRI. In 44% of the cases MY alone or combined with postmyelographic CT (pm-CT) showed a larger tumor extension than did MRI, while the opposite occurred in 25%. As for detection of bony metastases and tumor masses localized outside the spine there was no difference between MRI and MY + pm-CT. The results indicate that the choice between MRI and MY + pm-CT still can be based on the availability and quality of the procedure at a given institution.

In Denmark the hygienic quality of the bathing water has been controlled, based on general guidelines since 1978. Today more than 1100 control sites in marine areas have been established to ensure safe bathing water quality. According to EEC directives and Danish tradition, the control is usually performed by measuring the content of the indicator bacteria Escherichia coli (E. coli) in 5 to 20 test samples each bathing season.In Denmark, control programmes and data are evaluated using basic statistical quality control principles. This paper presents general guidelines for bacterial control, their statistical background and practical application. Furthermore, the evaluation and application of a specific programme for control of Staphylococcus aureus (S. aureus) are presented. This programme was used in a Danish bay where the authorities prescribe direct control of these potentially harmful bacteria.

We studied brain water self diffusion in pseudotumour cerebri by MR-imaging using single spin echo pulse sequences with pulsed magnetic field gradients of different magnitude. The methods is based on the fact that the movement of water molecules is restricted in brain tissue and that accumulation of water in the brain tissue will enhance the self diffusion of water. In order to evaluate the brain water content in pseudotumour cerebri we compared the water self diffusion coefficient in various regions of the brain in pseudotumour patients with that of healthy controls. Ten patients with pseudotumour cerebri were studied. All had increased ICP and increased resistance to CSF outflow. All patients had normal conventional MR spin echo images without focal lesions and a normal sized ventricular system. All patients had abnormal diffusion images showing increased water diffusion. Some patients had in particular increased diffusion in the periventricular regions, others in the whole brain. The diffusion coefficients in all brain regions of interest were significantly higher in patients than in controls. The findings suggest that patients with pseudotumour cerebri have a convective transependymal flow of water causing an interstitial brain oedema and in addition an intracellular brain water accumulation.

We reviewed all medical records concerning patients suffering from spinal cord or cauda equina compression (SCC) secondary to cancer, in the eastern part of Denmark, from 1979 through 1985. During the period the incidence of SCC in cancer patients went up from 4.4% to 6%. However, this increase was not significant. The series comprised 398 cases, with carcinoma of the prostate (19%), lung (18%), breast (14%) and kidney (10%) accounting for 61%. The symptoms were evaluated in accordance with the patients rating of pain, motor deficits, sphincter control and paraesthesia, whereas the clinical manifestations were classified on the basis of motor deficit and bladder dysfunction. During the period preceding the diagnosis of SCC, 83% of the patients suffered from back pain, 67% from deteriorating gait and 48% had retention of the urine. In 35% of the patients there was no sphincter disturbance and 10% had normal sensory function. The outcome of treatment was estimated by changes in motor deficits and sphincter function, and depended primarily on the patients condition at the time of the diagnosis. Of the patients who were able to walk before treatment, 79% remained ambulatory, whereas only 18% of the non-ambulatory patients regained walking ability. Patients treated by decompressive laminectomy followed by radiotherapy apparently had a better response than patients treated with surgery or irradiation alone, but when the patients pre-treatment motor function was taken into account, no significant difference was observed. The study may call for a properly randomized trial with careful stratification of tumour biology, performance status and neurological deficits.

CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n = 15), NA (n = 10) and DA (n = 10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n = 9) were similar at the two sites. A significant positive correlation between the concentrations measured at the two levels was found for VIP (rs = 0.65; p less than or equal to 0.01) and DA (rs = 0.94; p less than or equal to 0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (rs = -0.76; p less than or equal to 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (rs = -0.75); p less than or equal to 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH.

Resistance to CSF-outflow (Rout) and intracranial pressure (ICP) were measured in 33 patients with hydrocephalus after subarachnoid haemorrhage (SAH). Eleven patients examined between 10 to 30 days after SAH had high pressure hydrocephalus (HPH). Twenty-two patients had normal pressure hydrocephalus (NPH). All HPH-patients had ICP above 15 mmHg, plateau waves and B-waves, a median Rout of 59 mmHg x ml-1 x min-1 (range 29-100). All NPH-patients had a normal ICP level, no plateau waves, but long periods of B-waves and a median Rout of 22 mmHg x ml-1 x min-1 (range 6-47). Of the 11 patients with HPH six were shunted and five had temporary ventricular drainage. Five patients improved and six died. Of the five survivors only one went back to work. Of the 22 NPH-patients 18 were treated with a shunt, one refused shunt operation and three had normal Rout. Seventeen improved after shunting. At follow-up 12 had a normal social life, 5 lived in a nursing home and 1 was dead. Thus, early development of hydrocephalus after subarachnoid haemorrhage is associated with a high Rout and a high ICP, whereas late (more than one month) hydrocephalus may be associated with normal ICP and high Rout. Patients with NPH and a high Rout have frequent B-waves and should be shunted. Patients with a long interval from subarachnoid haemorrhage to the diagnosis of hydrocephalus often have a normal ICP, low frequency of B-waves, normal CSF-dynamics and need no shunting.

The response of plasma and ventricular cerebrospinal fluid vasopressin concentration to short-time induced intracranial hypertension was studied in 8 patients with hydrocephalus, defined as ventricular enlargement on computerized tomography. In connection with measurement of conductance to cerebrospinal fluid outflow, the concentration of vasopressin in plasma and cerebrospinal fluid was measured during perfusion at a low (less than 10 mmHg) and at a high (greater than 20 mmHg) intraventricular pressure level. Mean plasma vasopressin concentration was increased from 2.4 +/- 0.4 pg/ml (SEM) during perfusion at the low pressure level to 4.2 +/- 0.8 pg/ml (p less than 0.01) at the high pressure level. The cerebrospinal fluid concentrations of vasopressin at the low and high intraventricular pressure were 1.2 +/- 0.1 pg/ml and 1.7 +/- 0.2 pg/ml (p less than 0.05), respectively. However, only half of the patients responded to the increase in intraventricular pressure with an increase in cerebrospinal fluid vasopressin concentration exceeding 50%. The results of the present study suggest that an increase in the intracranial pressure might be a stimulus for vasopressin release in both the blood and the cerebrospinal fluid.

Four patients are described presenting papilloedema, increased pressure and reduced CSF absorption--caused by either spinal tumours, leptomeningeal carcinomatosis or encephalitis. Remarkably they all had a normal CT without signs of hydrocephalus. A 24-hour intracranial pressure monitoring showed a mean pressure of 30-35 mm Hg, recurrent plateau waves and high occurrence of B waves. Conductance to CSF outflow studied by a constant perfusion test was severely reduced 0.010-0.026 ml min-1 mm Hg-1 (normal greater than 0.12 ml mm Hg-1 min-1). Despite these findings no ventricular enlargement was seen on serial CT scans. The reason therefore remains unknown. Disappearance of papilloedema and a variable clinical improvement followed shunt-insertion.