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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.

Four patients with typical manifestations of herpes simplex encephalitis were treated with Aciclovir. Infection with herpes simplex virus was confirmed in three of the four cases. Complete cure was achieved in each of the patients despite severe initial disease patterns. In view of these results in the treatment of a disease that had so far been partly lethal or produced severely defective states, the specific use of Aciclovir is emphasised.

Objective: To assess the efficacy of Clostridium botulinum type A toxin-hemagglutinin complex [BoNT-A, Dysport®] in the treatment of adults with adductor muscle spasticity due to definite or probable multiple sclerosis [MS].Methods: In this 12-week multinational, randomized, double-blind, placebo-controlled trial, patients received a single treatment of either BoNT-A 1,000–1,500 Ipsen units or placebo injected into the adductor muscles of each leg [500–750 Ipsen units per leg]. The primary outcome measure was a novel, patient-selected, functional outcome measure at week 4.Results: Fifty-five subjects were treated with BoNT-A, and 51 received the placebo. Treatment benefit in favor of BoNT-A, which tended toward significance, was seen for most endpoints but not the subjective patient-selected key outcome measure. As with a previous dose-ranging study of BoNT-A, pain was significantly reduced in both legs [P < 0.05 at weeks 8 and 12]. Lack of significance for the other endpoints was probably due to the low ...

Homonyme Gesichtsfeldausfalle fuhren zum Verlust der Fahrerlaubnis, wenn sie naher als 30 Grad an das zentrale Sehen heranreichen. Als Referenzmethode der Gesichtsfeldbestimmung gilt die kinetische Perimetrie. Operative Eingriffe am Temporallappen fuhren zu homonymen Anopsien, sie betreffen, wenn wenig Fasermaterial der Sehbahn geschadigt wurde, den temporalen Halbmond des oberen kontralateralen Quadranten. Reicht die Schadigung tiefer bis in die Nahe des Temporalhorns, resultiert eine homonyme Anopsie des oberen Quadranten oder zusatzlich auch von Teilen des unteren. Bei den Eingriffen muss berucksichtigt werden, ob die damit moglicherweise erreichte Anfallsfreiheit aufgrund des Gesichtsfeldausfalles mit dem endgultigen Verlust der Fahrerlaubnis erkauft wird.

We performed a cross-sectional, “bottom-up” observational study of resource use, costs, and quality of life in patients with multiple sclerosis (MS) in Germany. Six centers participated in the study. Patients were asked to complete a questionnaire, and a total of 737 patients returned it (response rate 66%). The questionnaire provided information on all resource consumption, medical, and nonmedical, work absence, informal care related to their MS, and quality of life (EuroQol). Simultaneously, medical charts were also abstracted for a subsample of 202 patients for comparison between answers in the questionnaires and registered data. Levels of disability were assessed using the Expanded Disability Status Scale. The mean age of the cohort was 41.9±14.1 years (disease onset 33.4), mean EDSS score 4.4 (range 1.0–9.5), and mean utility measured by EQ-5D 0.552±0.331). Mean total cost per patient and year was 65,400 DM, adjusted for use of interferons, which was higher in this sample than the current average use in Germany. When this cost is extrapolated to an estimated patient population of 120,000, total costs to society are estimated at 7.85 billion DM. Direct costs represented 57.5%, informal care accounted for 12.1% and indirect costs amounted to 42.5%. Public payers pay for an estimated 24,800 DM per patient or 38% of total costs. All types of costs (direct, informal care, indirect) increased with increasing disability, while utilities decreased.

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.

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.

To improve the serodiagnosis of erythema migrans, we evaluated how sensitivity and specificity of immunoblotting are influenced by antigen concentration and blocking conditions. We found that an antigen concentration of 0.5 micrograms per lane in concert with ovalbumin blocking of the nitrocellulose provided the best results. In this case, 81% of the erythema migrans had positive immunoglobulin M tests, whereas only 33% were positive in a flagellum enzyme-linked immunosorbent assay (ELISA) and 28% were positive in a sonicate ELISA.

The paramedian diencephalic syndrome is characterized by a clinical triad of hyper-somnolent apathy, memory loss, and abnormalities of vertical gaze. The authors introduce a patient with the typical syndrome of paramedian thalamic artery infarction. The extent of the infarction was studied by MR imaging. Bilateral infarcts of the medial thalamus-accounting for the behavioral syndrome-and lesions in the area of the rostral interstitial nucleus of the medial longitudinal fasciculus-accounting for the vertical gaze palsy-were identified.

Overlapping decapeptides based on the flagellin sequence of Borrelia burgdorferi B31 (G. S. Gassmann, M. Kramer, U. B. Göbel, and R. Wallich, Nucleic Acids Res. 17:3590, 1989) were used to identify immunologically reactive regions of flagellin. Five serum specimens from patients with late manifestations of Lyme disease and borrelia-specific monoclonal antibody H9724 reacted with an epitope in the central region of the flagellar protein (amino acids 205 to 226), which is heterologous to the amino acid sequences of other bacterial flagellins. This epitope was not recognized by human sera with antibodies to Treponema pallidum, sera of healthy individuals, or sera from patients with stage I or II of Lyme disease.

The first section of the paper presents the morphology, structure and function of the eosinophilic granulocytes, while the second part deals with major neurologic diseases in which eosinophils are present or represent significant findings. These data are compared with the results of the author's own examinations of 1,000 unselected cerebrospinal fluid (CSF) samples. Eosinophils appeared usually in conjunction with infection, followed by foreign body inflammation. If the proportion of eosinophils exceeds 4%, the condition is termed CSF-eosinophilia, which usually develops in the presence of foreign bodies. However, infection may produce similar findings, especially in parasitic disease, and tumours of the central nervous system occasionally present with CSF eosinophilia.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Autoimmune phenomena are of major importance in the pathogenesis of the main paraneoplastic diseases in humans. The autoimmune process is probably triggered by oncogenic antigens, which are cross-reactive or identical with certain neural antigens. Despite the known pathomechanism these syndromes are still considered as non-treatable. We report two cases of paraneoplastic cerebellar degeneration, in which intensive immunosuppression with cytostatics lead to considerable neurological improvement.

Liquorbefunde bei intrakraniellen und -spinalen Metastasen des Mammakarzinoms sind abhangig von ihrer Grose, vom Grad ihrer Malignitat, v. a. aber von der Lokalisation dieser Metastasen. Es ist keine Frage, das Metastasen im ossaren Kranium oder in der Wirbelsaule oder auch Metastasen in der Dura, pathologisch-anatomisch ein durchaus gewohnlicher Befund, keine Liquorveranderungen bewirken, es sei denn, es kommt durch diese Tumoren zu einer Zirkulationsstorung des Liquors. Nach der Autopsiestudie von Tsukada et al. [11] sind uber ein Viertel der zentralnervosen Metastasen allein in der kranialen Dura zu erwarten, werden also keine Veranderungen des Liquors hervorgerufen.

Die Formulierung des Themas impliziert, das visuelle wie auch andere Halluzinationen ihrem Wesen nach keine eigentlich neurologischen Symptome sind. Tatsachlich haben sich durch die weitgehende Trennung der Nervenheilkunde in ihre Teildisziplinen verschiedene Zustandigkeiten fur einzelne Symptome, so auch fur Halluzinationen entwickelt, Zustandigkeiten, die keinesfalls immer den klinischen Tatsachen entsprechen mussen.

Die Entwicklung der isoelektrischen Fokussierung (IEF) in Agarose- oder Polyacryl-amidgelen fuhrte zum Einsatz dieser Technik in der Liquordiagnostik (2). Bei entzundlichen Prozessen des Nervensystems findet man im Liquor u. a. oligoklonale Banden, die sich je nach verwendetem Trenn- und Farbeverfahren in unterschiedlicher Zahl und Intensitat zeigen (7).

In dieser Untersuchung werden in Anlehnung an fruhe Arbeiten (9,5) Liquorbefunde mit der klinischen Entwicklung vor und nach Lumbalpunktion (LP) korreliert. Folgende Fragen bestehen: 1. Gibt es in den Phasen eines Schubes (Verschlechterung, Plateauphase, Ver-besserung) verschiedene Liquorbefunde? 2. Lassen bestimmte Liquorbefunde Ruckschlusse auf die Prognose eines Schubes zu? 3. Gibt es in den verschiedenen Schubphasen unterschiedliche prognostische Marker?

Die isoelektrische Fokussierung von Serum- und Liquoreiweis hat sich zu einer der wichtigsten Methoden entwickelt, um verschiedene entzundliche Erkrankungen des ZNS nachzuweisen. Durch ihre hohe Sensitivitat hat sie die konventionelle elektrophoretische Trennung im Agargel im wesentlichen verdrangt. Zwei Methoden der Bandendarstellung haben sich in den letzten Jahren etabliert: die Farbung mit Coomassie-Blue und die Darstellung mit Silbernitrat. In den meisten Laboratorien wird wegen ihrer leichten Hand-habung die Coomassie-Blue-Farbung durchgefuhrt, manche Autoren empfehlen allerdings trotz groseren Zeit- und technischen Aufwandes die Silbernitratfarbung (1, 2,). Um die angeblichen Vor- und Nachteile herauszuarbeiten, haben wir in einer Untersuchungsreihe beide Methoden miteinander verglichen.

Auf der Zelloberflache von T– und B–Lymphozyten, naturlichen Killerzellen, Monozyten und manchen Gewebszellen konnen auf entsprechenden Reiz hin Rezeptoren fur Interleukin2 (11–2) ausgebildet werden. Auf den meisten frisch isolierten T–Lymphozyten von gesunden Probanden konnen Rezeptoren (I1–2 R) nicht nachgewiesen werden; werden sie allerdings polyklonal aktiviert, so kann man nach wenigen Tagen auf all diesen Zellen I1–2 R nachweisen (5). Die I1–2 R–Expression ist demnach das Zeichen fur eine fruhe T–Zell–Aktivierung. Eine verstarkte Expression von I1–2 R aus T–Lymphozyten des Blutes wurde bei Patienten mit MS beschrieben, die Befunde an Liquorzellen sind nicht einheitlich.

Entzundliche Reaktionen des ZNS werden uber eine Aktivierung des Immunsystems vermittelt, mesbar anhand von intrathekal synthetisiertem IgG. IgG-Index und oligoklonale Banden stellen zwei unterschiedliche Parameter zu dessen Bestimmung dar. Wir untersuchten beide Parameter anhand verschiedener diagnostischer Untergruppen, um mogliche Verteilungsunterschiede festzustellen.

Das Auftreten homonymer Gesichtsfeidausfalle bei multipler Sklerose gilt als seltenes oder ungewohnliches Symptom (2, 4, 6). Savitzky und Rangell (1950) halten eine homonyme Hemianopsie fur mit der Diagnose der multiplen Sklerose nicht vereinbar. Nach Ansicht dieser Autoren sind solche Gesichtsfeidausfalle immer die Folge weiterer zerebraler Erkrankungen. Wir berichten im folgenden uber funf Patienten mit einer multiplen Sklerose, bei denen homonyme Gesichtsfelddefekte Folge dieser Erkrankung waren. In alien Fallen lagen computer- und kernspintomographische Befunde des Gehirns vor. Auserdem wurde eine kinetische und eine statische Perimetrie durchgefuhrt.

The first section of the paper presents the morphology, structure and function of the eosinophilic granulocytes, while the second part deals with major neurologic diseases in which eosinophils are present or represent significant findings. These data are compared with the results of the author's own examinations of 1,000 unselected cerebrospinal fluid (CSF) samples. Eosinophils appeared usually in conjunction with infection, followed by foreign body inflammation. If the proportion of eosinophils exceeds 4%, the condition is termed CSF-eosinophilia, which usually develops in the presence of foreign bodies. However, infection may produce similar findings, especially in parasitic disease, and tumours of the central nervous system occasionally present with CSF eosinophilia.

The reaction of cerebrospinal fluid (CSF) granulocytes in the nitroblue-tetrazolium test (NBT test) was evaluated. In a previous study, methodological problems were resolved, and the method developed byPark et al. was modified to suit the special conditions of the CSF. Thirty-eight CSF specimens from 26 patients were analysed. It appears that NBT test results with CSF granulocytes are significantly positive — according to the criteria developed byPark for blood granulocytes — when bacterial meningitis is present. If the cause of the pleocytosis is not bacterial in nature, then the test results are negative in most cases, provided that the CSF sample contains little or no blood. The NBT test in bloody CSF may produce positive results no matter what the cause of the pleocytosis. Our results suggest that the NBT test is a general, non-specific indicator of granulocyte stimulation. It reflects the ability of granulocytes to react to a stress situation of the organism. Bacterial infection results in a conspicuously large number of stimulated (i. e. NBT positive) granulocytes.

The relation between lactate concentration and cell count was determined in 394 CSF samples from unselected patients. In addition, a similar analysis was performed in 156 CSF samples from patients with bacterial and non-bacterial meningitis. The correlation between cell type and lactate level was also examined. The analysis demonstrated a significant linear increase in lactate showing high lactate levels at cell counts above 350 cells per microliter. Since the lactic acid concentration in bacterial meningitis increases linearly with the number of lactate-producing cells, it may be concluded that the increased lactate concentration results from CSF pleocytosis. If lactate levels are higher than the normal distribution, additional sources of lactate production such as cerebral hypoxia must be assumed.