Incidence of multiple sclerosis in the urban area of Erfurt, Thuringia, Germany.

European data on the epidemiology of multiple sclerosis (MS) reveal a continuous increase in the incidence of MS, which does not as yet seem to have reached a plateau at any point in time. No epidemiological data are available from Thuringia, which belonged to the former German Democratic Republic and which was politically separated from the neighbouring epidemiologically well-known areas of Hesse and Lower Saxony. We determined the incidence of MS in the urban area of Erfurt in Thuringia, by prospective identification of patients, with a diagnosis of definite or probable MS between 1998 and 2002. The crude annual incidence was 8.0:100,000, which is the highest rate ever reported for Germany. Our data, showing a high proportion of females with a late disease onset, suggests an increase in female cases with a benign form of MS resulting in an increase in MS incidence. An impact of changing diagnostic procedures inflating the rate has still to be taken into account. Until now it is partly up to speculation whether the observed increase in incidence may be related to emerging new cases, possibly from the pool of prior subclinical MS cases.

Further evidence for Borrelia burgdorferi infection in morphea and lichen sclerosus et atrophicus confirmed by DNA amplification.

We present further evidence in support of the notion that Borrelia burgdorferi is possibly involved in the pathogenesis of morphea and lichen sclerosus et atrophicus (LSA). Running a nested polymerase chain reaction (PCR) with a primer set specific for the flagellin gene of B. burgdorferi enabled us to demonstrate the presence of Borrelia DNA in skin biopsies of patients with morphea (nine of nine) of LSA (six of six). Biopsy specimens obtained from patients with erythema chronicum migrans (two patients, four of four samples) and acrodermatitis chronica atrophicans (one patient, one of one sample) also showed positive PCR results. By contrast, there was no amplification of Borrelia DNA in control biopsies either from patients with chronic eczema (three of three) or psoriasis (two of two) or from normal skin (three of three). Antibodies directed against B. burgdorferi were only detected in the serum of patients with erythema chronicum migrans (two of two) and acrodermatitis chronica atrophicans (one of one) but were not present in cases of morphea (five of five), LSA (three of three), or in control subjects (three of three). These data suggest that B. burgdorferi may play a role in the pathogenesis of both morphea and LSA. Furthermore, we conclude that PCR analysis provides an important diagnostic tool, even in seronegative Borrelia infections.

T-cell subsets in the cerebrospinal fluid and blood of patients with multiple sclerosis.

The absolute numbers and ratios of helper/inducer (T4) and cytotoxic/suppressor (T8) T-cells were determined in cerebrospinal fluid (CSF) and blood of patients with multiple sclerosis (MS) and various other neurologic diseases (OND). In patients with MS, the T4:T8 ratio was higher in both blood and CSF, and the increase was significantly greater in CSF than in blood. These findings were due to an increased proportion of T4-lymphocytes in the CSF and to a decreased proportion of T8-cells in blood. These results indicate the need for additional studies of CSF lymphocytes in patients with MS.

Oligoclonal bands in serum and cerebrospinal fluid of patients with HIV infection.

Matched samples of serum and cerebrospinal fluid (CSF) from 15 human immunodeficiency virus (HIV)-infected patients were examined after isoelectric focusing. The appearance of oligoclonal bands only in the CSF could indicate the primary HIV infection of CNS in early stages of the disease. Later, the increasing number of autochthonous oligoclonal bands in the CSF suggested locally synthesized IgG against opportunistic infections. Because of the immunodeficiency, T cell independent polyclonal B cell stimulation might mask the oligoclonal pattern.

Peduncular hallucinations.

Peduncular hallucinations usually present as visual disorders and are often genuine hallucinations associated with thalamic and/or mesencephalic lesions. In this case report we describe the clinical findings in a patient with hallucinations. Magnetic resonance imaging demonstrated bilateral ischaemic lesions in the thalamus and in the mesencephalon. The pathogenesis of hallucinations in these disorders is discussed in the light of the findings provided by imaging techniques.

Homonymous paracentral scotomas.

Of 230 patients with homonymous visual field defects of central origin, 3 had paracentral scotomas. All complained of severe photophobia and difficulty in reading. Two patients suspected that the scotoma had developed as a result of glare; the visual disorder resolved in these cases, but persisted in the third patient. With the exception of the visual field defect defined by perimetry, no neurological or neuropsychological deficit were found. The scotomas was attributed to generalized cerebral hypoxia in two cases but remained undefined in the third patient. A lesion in the striate region was suspected, but imaging procedures did not show any abnormalities.

Cell count and ratio of helper/inducer to suppressor/cytotoxic T-cells in the cerebrospinal fluid of patients with multiple sclerosis.

The cell count and the helper/inducer to suppressor/cytotoxic T-cell ratio (T4:T8) in cerebrospinal fluid (CSF) were compared in patients with multiple sclerosis (MS) and other neurological diseases. The T4:T8 ratio was higher in patients with MS than in patients with other neurological diseases. A low or normal CSF cell count was associated with a more significant increase in the T4:T8 ratio in patients with MS. These findings imply that the increased T4:T8 ratio found in MS is masked by an inflammatory pleocytosis or that the shift appears only when pleocytosis is absent.

Combined application of cytodiagnostic technics to the cerebrospinal fluid.

The major purpose of the examination of the cells in the cerebrospinal fluid (CSF) is the diagnosis of malignant growths. However, unequivocal tumor cell diagnosis is often problematical, since cells of local origin can also demonstrate considerable proliferative activity and great morphological variety. In these circumstances, it is advisable to evaluate cells from several points of view. One can demonstrate morphological characteristics with panoptic staining and can gain an impression of the RNA content of a cell with acridine orange (AO) fluorescent stain. Quantitative measurements of DNA synthesis in vitro can be made by labelling with tritiated thymidine. Multidimensional cytodiagnosis gives a comprehensive impression of the quality of the cells in question and provides the clinician with information which can be valuable for subsequent diagnostic and therapeutic efforts.

Oligoclonal gamma-globulin banding of cerebrospinal fluid in patients with subacute sclerosing panencephalitis. Comparison of the electrophoretic pattern with that in multiple sclerosis and congenital infections.

Lumbar cerebrospinal fluid (CSF) of 8 patients with subacute sclerosing panencephalitis (SSPE) was examined by agarose gel electrophoresis. In comparison with normal controls and children with different neurological diseases (including infections, tumours and degenerative diseases) the quantitative evaluation of the pherograms by an analog computer revealed an extreme change of the gamma-globulin profile. All cases showed 6-7 abnormal subfractions consisting of 2-4 tall, markedly protruding spikes and several small intermediate fractions. The oligoclonal gamma-globulin contributed 20.1-42.5% to total protein. This particular gamma-globulin profile seems to be highly indicative of the diagnosis of SSPE. It can be distinguished from the oligoclonal pattern in patients suffering from multiple sclerosis (MS) and congenital infections. The CSF protein profile of 13 patients with MS was different from that in SSPE in that it showed 1-5 monoclonal gamma-fractions in every case with none or only one peak protuding more markedly. The percentage of all subfractions amounted to 4.5-23.8% of total protein. As in MS, the aspect of oligoclonality in 9 children with congenital infections (cytomegalic inclusion body disease, toxoplasmosis and rubella) was quite variable, as again 1-5 abnormal subfractions were detected. Their relative concentrations, on the whole ranging from 0.6-12% of total protein, was considerably lower than in SSPE.

Low interleukin-10 production is associated with higher disability and MRI lesion load in secondary progressive multiple sclerosis.

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.

Genotype-phenotype analysis in early-onset Alzheimer's disease due to presenilin-1 mutations at codon 139.

Mutations in the presenilin-1 (PS-1) gene are the main cause of autosomal-dominant early onset Alzheimer's disease (EOAD) and show a high penetrance of symptoms. There are more than 100 mutations in the PS-1 gene. Among them are at present four different missense mutations known at position 139 on exon 5. Lack of genotyping in other family members may lead to the suggestion of sporadic cases. We present the case of a 46-year old German female with EOAD. Cognitive decline started at the age of 32, while myoclonic and tonic-clonic jerks occurred later. Disease symptoms were present in three generations of her family. Genetic analysis revealed the M139V mutation on exon 5 of the PS-1 gene. We compared the clinical data of this family with seven previously reported families and two sporadic cases with mutations at the codon 139. The genotype-phenotype analysis showed marked intrafamilial homogeneity, but interfamilial heterogeneity in relation to the onset, duration, and progression of the disease. Onset and duration were not correlated to the amino acid exchanged. Another modifying genetic or environmental factor is probable.

A method for concentrating cerebrospinal fluid cells.

The morphology of CSF cells changes in vitro rapidly. An optimal cytologic evaluation therefore requires special demands for the cell preparation. The cell concentration by means of the forced spontaneous sedimentation yields the best cytomorphologic results. A simple method for cell concentration has been described. Its application in two variations is determined by the cell content. In the first version the cells sediment spontaneously on the microscopic slide and in the second version on the membrane filter. The sedimentation is facilitated by the absorbent paper. This method is particularly suited for concentrating cultured cells and CSF cells, which have been incubated in the presence of tracer.

Fatigue, sleepiness, and physical activity in patients with multiple sclerosis.

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r=0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r=0.40), disease severity (EDSS, r=0.38), and disease duration (r=0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS>4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.

No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis.

Intravenous immunoglobulins (IVIG) have been effective in reducing multiple sclerosis (MS) disease activity and improving disability scores. However, the mechanism by which this beneficial effect is achieved remains unclear. An effect of IVIG on pro- and anti-inflammatory cytokines which are thought to play a role in the disease process - has been postulated in a number of animal and ex vivo studies. Hence, we performed a study on 34 patients with secondary progressive (SP) MS being treated with monthly IVIG or placebo for two years according to the protocol of the ESIMS study. Clinical outcome measures and cytokine production (interferon gamma, tumour necrosis factor alpha, interleukin-4 and -10) were recorded in all patients and compared with respect to the treatment group. Against our expectations, IVIG did not reduce the relapse rate or the progression of disability or cytokine production. Our data argue against an enduring immunomodulating effect of IVIG, at least in SPMS.

Pure homonymous hemiachromatopsia. Findings with neuro-ophthalmologic examination and imaging procedures.

The study describes neuro-ophthalmologic findings in two patients with brain infarction who developed homonymous hemiachromatopsia with resolution to pure homonymous achromatopsia in an upper quadrant. All other visual parameters were normal; only color perimetry was capable of demonstrating the visual disorder. The results are presented with special emphasis on the macular region. Computed tomography studies and magnetic resonance imaging revealed lesions in the caudal and medial occipitotemporal gyri as well as in adjacent cortical regions. The lesions were secondary to disordered circulation in a proximal occipitotemporal branch of the posterior cerebral artery. The anatomical findings and functional relations of color vision in man are discussed in the light of animal findings.

Complex visual hallucinations in the hemianopic field.

From 120 patients with an homonymous hemianopia 16 experienced complex visual hallucinations in the hemianopic field. The brain lesion was located in the occipital lobe, though damage was not limited to this area. Complex hallucinations appeared after a latent period. They were weak in colour and stereotypical in appearance, which allowed differentiation from visual hallucinations of other causes. Different behaviour after saccadic eye movement differentiated between complex visual hallucinations in the hemianopic field and visual auras of an epileptic origin.

Visual illusions and hallucinations.

Visual illusions and hallucinations may accompany a wide variety of disorders with many different aetiologies; therefore, they are non-specific phenomena. Lesions in the visual pathway may be associated with visual misperceptions. In these cases more exact information about the misperceptions--whether they are monocular or binocular, present in the whole visual field or a hemifield--may contribute to diagnostic accuracy and to a more comprehensive understanding of the patient and his state of mind. Illusions such as perseveration, monocular diplopia and polyopia, and dysmorphopsia may also occur in healthy individuals, but they are found most often in patients with epilepsy, migraine and stroke. These phenomena do not permit exact localization and definition of an aetiology, but lesions in the occipital and occipitotemporal regions near the visual pathway are involved in most cases. Hallucinations always represent a pathological form of perception. They are classified as unformed (photopsias) or formed (complex). Photopsias may be described in terms of colour, shape and brightness. Their wide variety makes it difficult, if not impossible, to arrive at an exact description of their aetiology, but it is possible to define their anatomical origin in some cases. Complex hallucinations suggest an occipitotemporal locus. Whether they appear in the whole visual field or in the hemifield may prove decisive in determining pathogenesis. A number of characteristics permit a rough classification of these phenomena. Complex hallucinations accompany physical illness and are susceptible to psychodynamic interpretation.

Cytology of neoplastic meningosis.

Where a leptomeningeal carcinomatosis is clinically diagnosed, evidence should be provided of tumor cells in the CSF. Not necessarily in the first specimen, but in the course of the illness. The staining of the cells with the Pappenheim method generally provides sufficient information about the cells. The identification of cells in metastases of epithelial tumours is not difficult for anyone with some experience. Identifying cells from primary brain tumours - which however only rarely cause meningosis - can sometimes be more difficult. Attention should be paid to whether the cells occur in clusters or singly. However, extreme caution is called for. The cytological monitoring of the CSF is an essential part of chemotherapy or radiation treatment.

[Autoradiographic findings in cerebrospinal fluid cells (author's transl)]. / Autoradiographische Befunde an Liquorzellen.

The report concerns the results of autoradiographic studies of cerebrospinal fluid cells. We investigated pleocytosis in cases of inflammatory diseases of the central nervous system, hemorrhage in the cerebrospinal fluid space, brain tumor and hemoblastosis, as well as in cases of undefined neurologic disease. Cerebrospinal fluid was incubated with tritiated thymidine. The results show that tumor cells have the highest labeling index and monocytes the lowest. Cells from primary brain tumors incorporate tritiated thymidine more rarely and less intensely than cells from cerebral metastases. Lymphocytes from inflammatory disease in infants may demonstrate a high labeling index.