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.

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.

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.

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.

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.

Ictal generalized rhythmic alpha activity during non-convulsive status epilepticus.

We investigated the repetitive manifestation of non-convulsive status epilepticus with an uncommon ictal electroencephalographic pattern observed in two patients suffering from epilepsy (aged 29 and 55 years). The patients had suffered from epilepsy since the age of 1 and 40 years, respectively. Interictal and ictal neurological, neuropsychological and electroencephalographic investigations were carried out. Non-convulsive status started and ended abruptly, clinically as well as electroencephalographically. The ictal electroencephalographic pattern was a monomorphic alpha activity with a generalized bilateral distribution. Altered responsiveness, sometimes eyelid myoclonia (in one patient) and amnesia were the most characteristic clinical findings during non-convulsive status. Intellectual development was delayed in the patient with early onset of epilepsy. However, this was not the case in the other patient, who developed memory impairment during the course of the disease. In both patients, lamotrigine added to valproate reduced the frequency of status epileptici significantly. Obviously, these patients suffer(ed) from a type of generalized non-convulsive status epilepticus with an uncommon electroencephalographic pattern.

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.

[Multiple sclerosis--current status of therapy]. / Multiple Sklerose--Aktueller Stand der Therapie.

The rational drug-treatment of multiple sclerosis on an immunological basis requires an acquaintance with the different forms of the disease course along with an understanding of the underlying pathomechanisms as well as a thorough knowledge of the chances and limitations of such a therapy. Besides some well established treatment regimens other approaches are presented which are currently evaluated in clinical trials and their effects and side effects are discussed.

Production and characterization of a polyclonal antiserum against Spiroplasma mirum (ATCC 29335).

Spiroplasma mirum (ATCC 29335), an American tick isolate, was cultivated and its purity was controlled using electron microscopy and Tricine-SDS-PAGE. In the SDS-PAGE analysis, the protein pattern of the antigen used revealed a polypeptide profile (35 bands) with an approximate molecular weight of 161 kDa to 10.5 kDa. This strain was used to immunize two rabbits. The produced antisera did not cross-react with Mycoplasma pneumoniae, Salmonella minnesota, Borrelia burgdorferi, Treponema pallidum but did still react in Western blot analysis with Spiroplasma mirum at a dilution of 1:128.000. This specific and sensitive antiserum was used to examine 72 midgut smears of Berlin ticks (lxodes ricinus) individually by direct immunofluorescence. In 26 samples, we could demonstrate fluorescent structures, but we were not able to culture spiroplasmas from these samples.

[Gasperini syndrome--differential diagnosis of peripheral facial nerve paralysis. Neurologic and imaging findings]. / Das Gasperini-Syndrom--eine Differentialdiagnose der peripheren Fazialisparese. Neurologische und bildgebende Befunde.

The Gasperini syndrome is a cause of peripheral facial palsy: In the following case report, a 75-year-old woman is described who presented with a peripheral left facial palsy. On examination left beating nystagmus was found with contralateral loss of pain and temperature affecting the right side of the body but sparing the face. The signs and symptoms corresponded to the Gasperini syndrome caused by a lesion in the dorsal caudal pons in the region of the anterior inferior cerebellar artery. MR imaging confirmed a lesion in this site.

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.

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.

[Clinico-genetic diagnosis of ataxia telangiectatica (Louis-Bar syndrome)]. / Klinisch-genetische Diagnose der Ataxia telangiectatica (Louis-Bar-Syndrom).

We describe the possible difficulties in getting the diagnosis "ataxia telangiectasia" using the example of a 16 years old girl. If cases of cerebellar ataxia in childhood present without classical symptoms, the diagnosis of ataxia telangiectasia should not be excluded before chromosome analysis. In our case, first signs of cerebellar ataxia were observed from the age of 11 years and we found only mild, atypical located and late onset telangiectasis. Other signs of the syndrome, such as elevated alpha-fetoproteine and deficiency of IgA or IgE could not be detected. Chromosome analysis, however, demonstrated a breakage syndrome with chromosome 14 to 7 translocation and established a firm diagnosis of ataxia telangiectasia. Patients with chromosome breakage syndromes including the Louis-Bar-syndrome have an increased risk for malignomas. Therefore chromosome analysis should be undertaken in cases of children with cerebellar ataxia, and frequent radiological examination avoided.

Prevalence of antibodies to Borrelia burgdorferi in serum and cerebrospinal fluid samples from patients with neurological disorders in Berlin.

Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological department were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by Western blotting a method for confirmation. 65 patients (8.1%) had serum IgG antibodies in ELISA and 22 of these patients (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titres in CSF by ELISA and 12 (1.5%) reacted in the Western blot. Clinical features of Bannwarth's syndrome were present in 12 patients (1.5%) and 4 patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were seropositive by both methods and 10 had elevated antibody activity in the CSF proved by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduced the number of false positive results but kept its standard in detecting antibodies in patients with active disease.

Inflammatory signs, antibody response and antigen detection in cerebrospinal fluid over the course of neuroborreliosis.

CSF and serum specimens were consecutively obtained from three patients with neuroborreliosis (stage I, II and III), CSF protein content, cell counts and differential, IgG index, oligoclonal bands and anti-B. burgdorferi antibodies were measured. Cerebrospinal fluid (CSF) was tested for Borrelia-DNA being present prior to and after antibiotic treatment. While DNA could be identified before ceftriaxone was administered, there were no more amplification products afterwards. The goal of this study was to compare the usefulness of serodiagnostic methods and the detection of Borrelia burgdorferi-DNA in patients with clinically confirmed neuroborreliosis to test the efficiency of antibiotic therapy.

[Correlation between neurologic disease and Borrelia burgdorferi antibodies in 800 paired serum/cerebrospinal fluid samples]. / Korrelation zwischen neurologischer Erkrankung und Borrelia-burgdorferi-Antikörpern in 800 Serum/Liquorpaaren.

Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological clinic were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by a Western blot, a method for confirmation. 65 patients (8.1%) had serum IgG antibodies on ELISA screening and 22 of these (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titers in CSF by ELISA and 12 of these (1.5%) reacted to the Western blot. Clinical features of Bannwarth's syndrome (BS) were present in 12 patients (1.5%) and four patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were positive in serum by both methods and 10 had elevated antibody activity in the CSF proven by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduces the number of positive results but is sensitive in detecting active disease.

Meningitis with Burkitt like B-cell lymphoma in HIV infection.

Malignant lymphoma with meningeal involvement was detected in 7 patients with stage IV HIV infection. The diagnosis of lymphoma was made at a maximum of four months before discovery of meningeal involvement. In our seven cases the lymphoma was B-cell type, one case expressed Kappa chains, four cases demonstrated Lambda chains and in two cases differentiation was not possible. A review of findings in all HIV positive patients treated in the same period revealed 10 non-Hodgkin lymphomas of the B-cell type, though meningeal and cerebral involvement was observed only in B-cell lymphoma of the Burkitt type.