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Summary Background Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. Methods In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam–Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. Findings We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (−0·03 points [4·04]; −0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. Interpretation 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. Funding German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

The relevance of additional findings was examined in 50 patients in whom multiple sclerosis had been diagnosed. Magnetic resonance (MR) technique revealed morphological changes in 49 patients (688 foci), whereas CT scan visualised foci with modified enhancement in 35 patients only (133 foci) (70%). Oligoclonal antibodies were found in the CSF of 96% of the patients as pointers towards the inflammatory immunological process. Enhanced daily IgG production was seen in 57-70% of the patients, whereas in 52% stimulated lymphocytes were identified in the CSF. Total protein content and cell count in the CSF differed in only 22 and 26%, respectively. Functional deterioration of the myelin sheath resulted in 72% of MS patients in an increased latency of visually evoked potentials. Hence, oligoclonal antibodies in the CSF and multiple foci revealed by MR are the most reliable additional findings in MS and should be considered as essential aids to confirm the diagnosis. A modified schema is suggested in which CT is replaced by MR and the proof of oligoclonal antibodies is given a higher ranking. Pathological changes in evoked potentials are relevant only if clinical symptoms are absent. Sensitivity disturbances and manifestations of brain stem disorders are somewhat less significant.

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman was admitted with a 14-day history of general malaise, subfebrile temperature, radicular dysaesthesias in the "riding breeches" area, severe pain in the lumbar region and progressive disorders of bladder and rectal emptying. Physical examination showed a conus-cauda syndrome. Differential diagnosis was between myelitis (inflammatory or infectious), space-occupying intraspinal mass or vascular lesion. INVESTIGATIONS: Cerebrospinal fluid contained 1700/3 cells and there was intrathecal antibody synthesis against varicella zoster virus (VZV) and positive VZV-DNA analysis in the polymerase chain reaction. Magnetic resonance imaging of the lumbar spine revealed an inflamed enlarged conal and epiconal area with small haemorrhagic spots. There was no evidence of an underlying immune-modulated disease. TREATMENT AND COURSE: With the diagnosis of varicella zoster myelitis with cutaneous changes having been established the clinical signs and symptoms regressed almost completely with aciclovir administration (10mg/kg intravenously for 14 days). CONCLUSION: VZV without cutaneous involvement should be considered in the differential diagnosis of the radicular pain syndrome. When clinical signs of beginning myelitis or encephalitis are present, immediate investigations and therapy are necessary.

Item does not contain fulltext Abnormalities in T-cell-derived cytokine production are a well-known phenomenon in multiple sclerosis (MS). An association between disability and the production of interferon gamma has been demonstrated recently. The present study investigated associations between disability, cytokine production in stimulated blood lymphocytes and magnetic resonance imaging data in 37 patients with the secondary progressive course in the stable phase of the disease. Patients with high interleukin-10 (IL-10) production had significantly lower disability scores (p=0.009) and lower T2 lesion load (p=0.03). Interleukin-10 might not only play a role in the pathological process of multiple sclerosis but has an impact on disease outcome as well.

We describe a case of Guillain-Barré syndrome (GBS) in a patient with non-Hodgkin's lymphoma (NHL). A 21-year-old woman with a newly diagnosed stage IV high-grade lymphoma (precursor T-cell NHL according to the R.E.A.L. Classification) developed flaccid quadriparesis and bilateral facial diplegia after three weeks of treatment with vincristine, daunorubicin, L-asparaginase and prednisolone. The clinical course and neurological examination were consistent with GBS. Despite treatment with intravenous immunoglobulins her neurological symptoms progressed. Plasmapheresis was therefore initiated followed by intravenous immunoglobulins. After partial remission of neurologic symptoms, induction chemotherapy with cyclophosphamide and cytarabine was continued without any further complication. Three months later, the lymphoma was in complete remission. GBS has been described in Hodgkin's disease and after bone marrow transplantation but is rare in NHL. In patients with NHL who develop neurological symptoms, drug toxicity and nervous system infiltration are the leading cause of neuropathology, but GBS should be considered in the differential diagnosis.

The proinflammatory cytokine interferon gamma (IFG) is elevated in body fluids of multiple sclerosis patients but its variation range is broad. The reason for this wide scatter of IFG production is not yet known. We looked for the relation between clinical parameters such as disability, exacerbation frequency, disease duration, course of the disease and IFG producing blood lymphocytes. Forty-one consecutive, clinically stable multiple sclerosis patients with primary relapsing course of the disease and without immunomodulatory or immunosuppressive treatment in the last 3 months were investigated for IFG in blood lymphocytes by flow cytometry. A significant positive correlation between IFG production and disability (r = 0.45, P50.01, Spearman's rho coefficient) was found. Pathophysiological implications and therapeutical relevance of this unexpected finding are discussed.

A patient with a stage IV mantle cell lymphoma (according to the REAL classification) was treated with high-dose chemotherapy and autologous bone marrow transplantation. One year later while on alpha-interferon immunotherapy she suffered from progressive loss of short-term memory and reported difficulties in recognizing objects. Magnetic resonance imaging (MRI) showed a vast ring-enhancing lesion of the left postcentral parietal area. Serial stereotactic biopsies disclosed progressive multifocal leukoencephalopathy without JC-virus in the cerebrospinal fluid. Therapy with subcutaneous interleukin-2 (IL-2) every other day and intrathecal cytarabine once a week was started. After 4 weeks the patient refused further treatment. Nevertheless her condition improved over the next 8 months and MRI scans showed a marked improvement in the lesions.

Two cases of opportunistic cerebral infections in HIV-negative cancer patients due to chemotherapy induced immunosuppression are reported. A 61-year-old patient with low grade lymphoma (immunocytoma as referred to the Kiel classification) developed stereotactical biopsy proven toxoplasmic encephalitis 6 months after initiation of fludarabine treatment. The lymphoma had been diagnosed 8 years earlier and had been treated with several different regimens. In the second case, a 55-year-old patient developed neurological symptoms while in complete remission from acute T-cell leukaemia. The patient had been treated with a multidrug chemotherapy regimen including radiotherapy of the brain and intrathecal chemotherapy. When toxoplasmic encephalitis was bioptically diagnosed the patient was on maintenance chemotherapy with methotrexate and mercaptopurine for 12 months. The patients' characteristics and outcome are reported and the potential pathogenesis is discussed.

Objective: We studied the individual course of interferon gamma producing blood lymphocyte count (IFGC) of 15 multiple sclerosis patients started on 8 MIU beta interferon administered subcutaneously each other day. Methods: Mononuclear blood cells were prepared before treatment and on day 3, 9, 15, as well as after month 1, 2, 3 and 4 of therapy. After stimulation intracellular interferon gamma was detected with monoclonal fluorescent antibodies and measured by flowcytometry. IFGC is given as percentage of all gated lymphocytes. Results: forty-eight hours after first interferon beta application the mean IFGC dropped significantly from 11.37 to 7.09 (P

Generally, inflammatory demyelinating diseases selectively affect either the central or peripheral myelin. Here we report a case of a severe combined central and peripheral demyelination, each of which contributed equally to the clinical syndrome. A 32 year old female was admitted to a general district hospital with a 3 day history of aches in the legs, fever (38 °C), urinary retention and leg weakness. Neurological examination revealed a flaccid tetraparesis with abolished abdominal and ankle reflexes, diminished knee reflexes, bilateral extensor plantar responses, and sensory level at T12. The patient was given high dose intravenous prednisone (1 g) for 5 consecutive days. She became bedridden with complete paraplegia of the legs and was referred to our department. Upon admission, in addition to a flaccid tetraparesis (strength 1/5 in the legs and 4/5 to 4±5 in the arms, MRC grade) with abolished abdominal, knee and ankle reflexes, extensor plantar responses, and sensory level at T5, a bilateral gaze evoked nystagmus was detected. Urodynamic examination revealed an atonic bladder. Lumbar puncture revealed a pleocytosis (34/mm3; 84% lymphocytes) and a cerebrospinal fluid (CSF) protein of 132 mg/dl. Neither intrathecal immunoglobulin synthesis nor oligoclonal bands were detected. Complete microbiological and virological investigations on CSF and blood …

Mononuclear cell subsets in cerebrospinal fluid (CSF) and peripheral blood (PB) were monitored during the clinical course in 23 patients with acute meningitis using 6 monoclonal antibodies. Significant differences between aseptic and bacterial meningitis mainly consisted of a higher percentage of OKT4-positive cells in PB in the acute phase of bacterial meningitis. Significant differences between CSF and PB are found in the amount of most cell subtypes at all times except the acute phase of bacterial meningitis. The OKT4/OKT8 ratio was always significantly higher in CSF and correlated with the acuity of inflammation in bacterial meningitis.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

As response to interferon beta (IFNB) treatment, a 50% reduction of the mean relapse rate compared to pretreatment values has been reported. However, individual responses vary considerably, ranging from no reduction in exacerbation frequency to complete suppression of relapses for at least two years. At the moment, valid predictors for IFNB response are lacking. Here we present a prospective evaluation of 33 patients with primary relapsing multiple sclerosis, who were followed for two years of IFNB treatment. A low interferon gamma (IFG) production before treatment predicted a two-year term without exacerbations in 68.8% of cases correctly, whereas a high pretreatment IFG production implied the risk of at least one relapse in the first two years in 70.6%. These preliminary results encourage further evaluation of IFG as predictor of an IFNB treatment response.

We report a case of a 74-year old woman who following an acute virus encephalitis developed an akinetic-rigid Parkinson syndrome with tremor, hypokinesia, hypomimia, rigidity and cogwheel phenomenon in all four extremities, brady-dysdiadochokinesia as well as myoclonic jerks of the arms. Many of the clinical features of this postencephalitic parkinsonism (PEP) suggested the diagnosis of sporadic encephalitis lethargica, first described by von Economo 1917. Cerebral spinal fluid showed signs of a viral encephalitis, and a positive influenza A IgA-antibody titer (1 : >160) in the viral serologic screen was found. Positron emission tomography (PET) showed an altered pattern of glucose- and dopa-metabolism clearly different from findings in idiopathic Parkinson syndrome (IPS). The acute lack of inhibitory input from the substantia nigra pars compacta to the striatum could explain the different metabolic patterns in our case in comparison to IPS patients. Our findings indicate that PEP may also be caused by influenza A and furthermore that PET clearly distinguishes PEP from IPS.

A 43-year-old woman was admitted with a 14-day history of general malaise, subfebrile temperature, radicular dysaesthesias in the "riding breeches" area, severe pain in the lumbar region and progressive disorders of bladder and rectal emptying. Physical examination showed a conus-cauda syndrome. Differential diagnosis was between myelitis (inflammatory or infectious), space-occupying intraspinal mass or vascular lesion.Cerebrospinal fluid contained 1700/3 cells and there was intrathecal antibody synthesis against varicella zoster virus (VZV) and positive VZV-DNA analysis in the polymerase chain reaction. Magnetic resonance imaging of the lumbar spine revealed an inflamed enlarged conal and epiconal area with small haemorrhagic spots. There was no evidence of an underlying immune-modulated disease.With the diagnosis of varicella zoster myelitis with cutaneous changes having been established the clinical signs and symptoms regressed almost completely with aciclovir administration (10mg/kg intravenously for 14 days).VZV without cutaneous involvement should be considered in the differential diagnosis of the radicular pain syndrome. When clinical signs of beginning myelitis or encephalitis are present, immediate investigations and therapy are necessary.

Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, segmental arteriopathy of unknown etiology. Fibroplasia of the tunica media is most common. After the renal arteries, the carotid arteries are most frequently affected. Angiographically beaded and tubular stenoses are seen. Complete occlusions and spontaneous dissection of the carotid arteries occur. The angiopathy causes general symptoms such as headache and vertigo, but also recurrent TIA and ischemic cerebral infarction. We examined 15 patients (12 female) suffering from FMD and stroke. The diagnosis of FMD was based on angiographic findings in all cases. 13 patients made a good recovery and seven of them could be discharged from hospital without any neurological deficit. Apart from conservative treatment, primary percutaneous or operative angioplasty may be necessary in some cases in spite of the mostly benign outcome of the disease. Acetylsalicylic acid should be given in all cases.

Bei Leukamien und malignen Lymphomen im Erwachsenenalter mus in ca. 10 – 30 % mit einem sekundaren Befall der Leptomeningen gerechnet werden (5). Aueh die relativ seltenen, durch AIDS aber in letzter Zeit haufiger auftretenden primaren ZNS-Lymphome, die fruher 1 – 2 % aller Hirntumore ausmachten (4), neigen zur meningealen Aussaat und lassen sich dann durch eine liquorzytologische Untersuchung nachweisen. Die Trefferquote der Liquorzytologie liegt in Studien, bei denen Autopsiebefunde zum Vergleich herangezogen worden, im Mittel bei 62 % – 70 % fur die sekundare Beteiligung und bei 45 % fur die primaren malignen Lymphome des ZNS (2, 3, 5).

Although intensive care medicine and chemotherapy of bacterial infections have made great progress during the last 30 years, therapeutic efficacy in bacterial meningitis in adult patients could not be improved. Retrospective analysis of 391 cases of adult bacterial meningitis between 1950 and 1985 shows no significant changes in etiology and only slight reduction in mortality. The course of the disease depends mostly on age, state of consciousness and CSF cell count. Cases of meningitis in HIV patients and cerebral tuberculosis have not been evaluated in this study.

Mollaret's recurrent aseptic meningitis is a rare disease of unknown etiology and excellent prognosis, characterized by short attacks of meningeal irritation, fever and pleocytosis with first polymorphonuclear, then mononuclear predominance. A case is reported, in which the characteristic so-called endothelial cells in the CSF were identified as monocytes with immunocytochemic methods. The remaining fraction of CSF cells mainly consisted of T-lymphocytes with a majority of CD4 positive cells and an increased portion of CD38 positive cells. Between attacks, patients are asymptomatic. The course is self-limiting. Specific treatment is unknown.

With the exception of some genetically determined neoplastic syndromes, the aetiology of human brain tumours is largely unknown. This is also true for CNS neoplasms in children. Their occurrence has been tentatively linked with prenatal exposure to environmental carcinogens but so far, no positive correlation has been established [35]. From observations both in humans and experimental animals it is known that the adverse effects of toxic compounds on fetal and postnatal development are not restricted to the causation of malformations. The first report on transplacental tumour induction in experimental animals was by Larsen in 1947 [28] who observed a high incidence of lung adenomas in the offspring of mice treated with urethane (ethyl carbamate) during the last three days of gestation. In 1964, Mohr and Althoff [31] reported an increased incidence of respiratory tract tumours in Syrian Golden hamsters after transplacental administration of diethylnitrosamine. At about the same time, the powerful perinatal neuro-oncogenic effect of ethylnitrosourea was discovered by Druckrey et al [5]. Since then, a great number of chemical carcinogens has been found to be similarly effective in a variety of experimental animals (Table 1). In 1971, Herbst et al. [17] and Greenwald et al. [11] reported the occurrence of vaginal adenocarcinoma in young women after maternal treatment with diethylstilboestrol (DES) but until now, DES has remained the only agent known to induce tumours transplacentally in humans.

Leukocyte subsets in CSF and peripheral blood (PB) were determined in 21 patients with acute inflammation of the CNS using the monoclonal antibodies OKT3, OKT4, OKT8, Leu12, and OKM1 in an immunoperoxidase slide assay. There was a predominance of OKT3-positive cells in nearly all samples. Significant differences between acute aseptic and bacterial meningitis only were found in CSF and represented by a higher Leu12 and a lower OKT3 percentage in aseptic inflammation and a higher absolute amount of OKT4-, OKM1- and Leu12-positive cells in bacterial meningitis. Comparison between CSF and PB showed significant differences only in aseptic meningitis with a higher percentage of Leu12-positive cells and a lower percentage of OKT8-positive cells in CSF. The OKT 4 OKT 8 ratio seems to be generally lower in aseptic meningitis but significant differences only were found in comparison with healthy blood donors. In a case of herpes simplex encephalitis the ratio was strongly increased in CSF during the early phase of specific antibody production because of an absolute rise of OKT4-positive cells.

A case of primary diffuse leptomeningeal melanoblastosis in a 46-year-old male is reported. His symptoms included headaches, transient hemiparesis, epileptic seizures and a progressive psychosyndrome. CT brain scans showed a slight enhancement of density in the subarachnoidal space. The disease was diagnosed by CSF cytology, using light microscopy, electron microscopy, autoradiography and cell culture. Systemic combined chemotherapy using Cisplatinum, DTIC, and Vindesine was without any significant response and he died 18 weeks after onset of the first complaints. Autopsy showed a diffuse infiltration of the entire leptomeninges by melanotic melanoblastoma cells invading the sagittal superior sinus. A thorough dissection including the orbital contents and skin nevi failed to reveal a primary tumor outside the CNS.

Adult male gerbils (Meriones unguiculatus) received a single s.c. injection of N-nitroso(methyl-14C) methylbenzylamine (2.5 mg/kg body weight). Of the radioactivity injected 46% was exhaled as 14CO2 within 8-10 hours and an additional 21% was excreted as urinary metabolites. Six hours after injection of the carcinogen, methylation of DNA bases was highest in lung (81.5 mumol 7-methylguanine/mol guanine) followed by liver, esophagus, kidney, forestomach, glandular stomach, spleen, colon and small intestine. The brain DNA no alkylation products were detectable. These data differ significantly from those obtained in rats and mice which under similar experimental conditions metabolized N-nitrosomethylbenzylamine preferentially in esophagus and liver respectively.