Surgical intervention and heparin-anticoagulation improve prognosis of rhinogenic/otogenic and posttraumatic meningitis.

It is still controversial, whether early surgical removal of infectious material and heparin-anticoagulation to reduce vascular complications will improve outcome in acute meningitis. In the present pilot-study 40 patients with acute or delayed post-traumatic or oto-/rhinogenic purulent bacterial meningitis were analysed for neurological outcome by using the Glasgow outcome score (GOS) and the Tuthill functional score; patients were treated either by early surgical revision of the septic focus (Group 1, within 6 days, n = 15), late surgery (Group 2, later than 6 days, n = 19), or no surgery at all (Group 3, n = 6). All patients, independent of surgical approach, received therapeutic heparin-anticoagulation. Patient groups were otherwise comparable for antibiotic treatment, osmotherapy, microbiology, CSF-findings, CT-scans and prognostic factors. Outcome according to GOS was superior in Group 1 compared with Groups 2/3 (non-significant). Although there was no significant difference on admission in the Tuthill functional score, Group 1 achieved a superior final outcome of 96 points compared with Groups 2 and 3, who gained 72 points (p < 0.01). In addition, Group 1 patients had significantly less intracranial complications (8/15 patients versus 21/25 patients in Groups 2/3, p < 0.01) and were dependent upon respirator treatment for fewer days (10.2 days) than Groups 2/3 (12.5 days, non-significant). In 31 patients CSF-leakage was identified: among these, 17 patients had CSF-leakage, which had not been anticipated by clinical/neuroradiological examinations and revealed only by surgery. The overall mortality in this study population was very low (2.5%), therefore, therapeutic heparin seems to represent an additional favorable treatment measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous-pressure controlled, external ventricular drainage for treatment of acute hydrocephalus--evaluation of risk factors.

Experience with a continuous-pressure controlled, external ventricular drainage system (EVD) in 100 patients (n = 49 female, n = 51 male; mean age, 56.3 yr) with acute hydrocephalus is reported. Cerebrospinal fluid circulation disturbances resulted from hemorrhages caused by subarachnoid hemorrhage (n = 45), parenchymal hemorrhages from angioma (n = 4), anticoagulants (n = 7), or hypertension or other reasons (n = 30); in addition, hydrocephalus developed from infections (n = 3), tumors (n = 2), infratentorial infarction (n = 5), or unknown reasons (n = 4); 52 patients had ventricular hemorrhages. No patient died of system-associated morbidity. Mean time of EVD treatment was 9.5 days, with 40 patients being treated for 10 to 29 days; routine refobacin (5 mg) flushing of the system was performed three times a day. Patients without cerebrospinal fluid leakage had a 2% rate of secondary infection compared with 13% in patients with cerebrospinal fluid leakage due to ventricular catheter placement (P < 0.05; overall infection rate, 5%). A clinical mortality rate of 29% during EVD treatment was observed in subarachnoid hemorrhage patients (Hunt and Hess Grades II, III, IV, and V; n = 9, 9, 18, and 9, respectively); recurrent hemorrhages during EVD treatment occurred in 19 patients (26 hemorrhages), and of these, 10 patients died. System occlusion was seen in 19 cases (12 of 45 patients with subarachnoid hemorrhage), requiring catheter and system renewal in 1 case; system extraction was seen in 3 cases, misplacement was seen in 11 cases, and disconnection was seen in 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurological long-term follow-up in left atrial myxoma: are late complications frequent or rare?

Neurological manifestations were analysed in 13 patients with left atrial myxoma confirmed by histological study. In this group, 6 patients had neurological complaints at initial presentation, 5 had cardiac symptoms, and 4 patients presented with signs of systemic disease. CT was performed in 10 and MRI in 7 patients. There were signs of ischaemic or haemorrhagic infarction (6 of 12) and one lesion suggestive of myxoma metastasis; other findings mainly comprised non-specific white matter lesions revealed by MRI. Neurological follow-up 0.5-8 years after tumour resection revealed no delayed neurological complications, follow-up CT and MRI findings were not suggestive of lesions acquired after operation. It is suggested that this rare condition of cardiac myxoma should be suspected in young patients with CNS symptoms or signs lacking cerebrovascular or cardiovascular risk factors and should be included in the differential diagnosis of vasculitis. With timely diagnosis and resection of the cardiac tumour the long-term prognosis can be considered improved.

Histopathological findings in the central and peripheral nervous systems in neuroborreliosis. A report of three cases.

Very little is known about tissue changes and pathophysiological mechanisms in Garin-Boujadoux-Bannwarth syndrome. We report histopathological findings in the central and peripheral nervous systems of three typical cases. In the acute stage of the disease mononuclear perivascular infiltrations with mainly T-helper cells were the prominent finding, whereas after treatment there was no vessel involvement. The fibre changes in the peripheral nervous system consisted of axonal degeneration. No Borrelia burgdorferi-specific antigen could be detected by immunohistochemical methods. Thus vasculitis might be one of the primary pathophysiological mechanisms for the involvement of the nervous system.

Borrelia burgdorferi myelitis presenting as a partial stiff man syndrome.

Eight weeks after a tick bite, a 33-year-old male patient presented with stiffness of one leg together with spasmodic painful jerks resembling stiff man syndrome. Isolated myelitis of lumbosacral segments of the spinal cord, apparently confined to the grey matter, was diagnosed and its spirochaetal aetiology confirmed by serology and CSF findings. Oligoclonal IgG bands in CSF specific for Borrelia burgdorferi were found. Thus, there is evidence that B. burgdorferi ist able to cause a localized myelitis, probably of spinal interneurons, presenting as a partial stiff man syndrome.

Panencephalopathic type of Creutzfeldt-Jakob disease with primary extensive involvement of white matter.

The case of a 66-year-old woman with atypical Creutzfeldt-Jacob disease (CJD) presents several peculiarities. Pathologic examination confirmed a rare CJD case with primary generalized spongiform changes of the white matter and only moderate, but typical changes of the gray matter. Besides an essentially typical clinical course, the patient developed temporary diplopia and vertical eye movement paralysis. Intoxication had been excluded. Isoelectric focusing revealed oligoclonal CSF-IgG. Magnetic resonance imaging studies showed periventricular accentuated flat and striped hyperintense structures. EEG had CJD-typical periodic 1/s synchronous discharges. This case illustrates for the first time that in panencephalopathic type of CJD the cerebral white matter can be involved primarily and more extensively than the gray matter.

A 10-year matched-pairs study comparing azathioprine and no immunosuppression in multiple sclerosis.

In a retrospective matched-pairs study the efficacy of azathioprine treatment was compared with no treatment over a period of at least 10 years. Of 277 patients with clinically definite multiple sclerosis seen during the years 1973 and 1974, 42 pairs were selected by similarity in disability score, sex, age and disease duration. Only 3 patients were lost to follow-up, and in 2 cases the initial diagnosis could not be confirmed. At the end of the 10-year period the number of wheelchair-bound, bedridden or deceased patients was double in the untreated as compared with the azathioprine-treated group but the number of non- or only minimally handicapped patients was similar in each group. The mean disability score was significantly lower in the treated group. Although caution is warranted as in every retrospective study because of insufficiently controlled confounding variables, these results support a positive but weak long-term effect of azathioprine.

Treatment of Lyme borreliosis. Randomized comparison of doxycycline and penicillin G.

Seventy-five patients with neurological symptoms of Lyme borreliosis were randomly assigned to intravenous treatment with either penicillin G or doxycycline. After 12 months the treatments were equally effective regarding the clinical picture and laboratory findings. No patient was considered to be a treatment failure. However, one-third of the patients showed delayed recovery, particularly after a longer primary disease duration. A slow recovery, lasting years, was typical of subacute or chronic borreliosis.

Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years.

In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an "immunological scar syndrome". Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.

Borrelia burgdorferi--specific and autoreactive T-cell lines from cerebrospinal fluid in Lyme radiculomyelitis.

In 3 patients with Lyme radiculomyelitis, cellular immune reactions of cerebrospinal fluid (CSF) lymphocytes were analyzed. Phenotypic analysis of CSF cells demonstrated that the majority were T cells (CD3+) of the helper/inducer subset (CD4+). These T cells were directly expanded from the CSF by limiting dilution. A total of 505 T-cell lines were tested for Borrelia burgdorferi (Bb)-specific proliferation and also partly tested for reactivity to a panel of central and peripheral nervous system antigens. Proliferative assays revealed 33 of them to be Bb specific, 16 to be specific for myelin basic protein, 16 to be specific for peripheral myelin, 1 to be specific for cardiolipin, and 2 to be specific for galactocerebrosides. The antigen-specific proliferation was restricted by autologous human leukocyte antigen (HLA) class II molecules. The majority of CSF-derived T-cell lines stained positively for CD3, CD4, and HLA class II antigens and negatively for CD8 (cytotoxic/suppressor subset). One T-cell line provided help for the production of specific IgG by autologous B cells and secreted gamma-interferon upon stimulation with Bb antigen in the presence of autologous antigen-presenting cells. These data show that in patients with severe neurological manifestations of late Lyme disease, not only Bb-specific T-cell lines but also T cells reactive to central or peripheral nervous system autoantigens can be found.

[Acute and chronic diseases in transmitted borreliosis by tick bite]. / Akute und chronische Erkrankungen bei zeckenvermittelter Borreliose.

We report on clinical and laboratory findings of 58 study patients with tick-bite burrelia burgdorferi-infection. In seven cases, chronic borreliosis like a tertiary metaluetic illness was recognized. All were treated either with high-dose penicillin intravenously or tetracycline. Results of treatment and recommendations are given.

Acute and chronic illness after tick-bite Borrelia burgdorferi-infections: results of treatment.

We report on clinical and laboratory findings of 28 patients with tick-bite Borrelia burgdorferi-infection. In 5 cases chronic tertiary metaluetic manifestations were recognized. All were treated either with high-dose penicillin intravenously or tetracycline. Results of treatment and recommendations are given.

Vidarabin-monophosphate, BCNU, VM26--an in vitro comparative study of active agents in the treatment of malignant human brain tumours.

BCNU (carmustine), VM26 (teniposide) and ARA-A5'P (vidarabin-monophosphate) were compared in their activity against 30 cell lines of primary (N = 21) and metastatic (N = 9) human brain tumours, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products c X t were correlated with in vitro pharmacokinetic data in order to evaluate in vitro drug sensitivity at relevant exposure doses. A microcytotoxicity assay was employed to screen for drug toxicity in individual tumour cell lines. Following drug exposure and 5 to 8 population doubling times of untreated controls, RNA-synthesis - as a parameter of cell metabolism and proliferation - was determined by incorporation of [5,6-3H]-uridine into cellular RNA (liquid scintillation counting protocol). The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index (SI); by these means effects of different drugs on individual tumour cell lines could be compared. Mean sensitivity indices of ARA-A5'P, BCNU and VM26 for primary brain tumour cell lines were 0.59, 0.82 and 0.54. ARA-A5'P and VM26 had almost similar activities against brain tumour cell lines, whereas BCNU was significantly (P less than 0.001) less active. High grade gliomas were less sensitive to all three agents than low grade and infratentorial gliomas. ARA-A5'P was also able to effectively reduce colony formation in brain tumour cell lines. A cross-resistance of ARA-A5'P to either BCNU or VM26 could not be observed. Clearly, ARA-A5'P is an effective drug in treatment of brain tumour cells in vitro.

Therapy of malignant brain tumors: comparison of the in vitro activities of vidarabin-monophosphate, BCNU and 5-fluorouracil.

BCNU (carmustine), 5-Fluorouracil (5-FU) and Vidarabin-monophosphate (ARA-A5'P) were compared in their activities against 30 cell lines of primary (n = 21) and metastatic (n = 9) brain tumors, which were characterized in tissue culture by cytochemical, immunological and cytogenetic criteria. In vivo achievable concentration-time products were correlated with in vitro pharmacokinetic data. A micro assay was employed to screen for drug toxicity in individual tumor cell lines; cells were exposed to the drugs at exposure doses relevant to in vivo pharmacokinetics. After 5-8 population doubling times of untreated controls, RNA-synthesis, as a parameter of cell metabolism and proliferation, was determined by incorporation of (5, 6-3H)-uridine into cellular RNA (liquid scintillation counting protocol). A tumor stem cell assay was performed under similar conditions. The cytotoxic effect of each drug on individual cell lines was expressed in terms of a sensitivity index SI (SI = 1 indicating complete resistance) to compare effects of different drugs on the individual tumor cell lines. Mean sensitivity indices for ARA-A5'P, BCNU and 5-FU in brain tumor cell lines (in brackets: primary CNS-tumors) were 0.64 (0.59), 0.89 (0.82) and 0.35 (0.33) respectively. 5-FU was significantly more active than BCNU and ARA-A5'P (P less than 0.001), whereas BCNU was significantly less active than ARA-A5'P (P less than 0.001). ARA-A5'P had a suppressive effect on formation of brain tumor stem cell colonies. There was no cross-resistance of ARA-A5'P to either BCNU or 5-FU. We conclude that ARA-A5'P and 5-FU are potent agents in experimental therapy of human brain tumors, compared with BCNU.

Local hemostasis in subarachnoid hemorrhage.

Fibrinopeptide A (FPA), platelet-secreted protein, platelet factor 4 and beta-thromboglobulin were determined in the cerebrospinal fluid of patients who had suffered from subarachnoid hemorrhage and were treated with 6 g tranexamic acid or 4 million KIU aprotinin to prevent rebleeding. Platelet-secreted proteins and FPA were cleared from the cerebrospinal fluid within 3 days after bleeding. Their vasoactive and thrombotic capability is limited to the initiation period of vasospasm that usually comes to clinical observation 3-8 days after bleeding. Increased thrombotic activity of the cerebrospinal fluid, as reflected by high levels of FPA and platelet-secreted protein, seemed to promote the occurrence of neurological deficits.