[Irreversible brain death-Part 2. Spinalization phenomena]. / Irreversibler Hirnfunktionsausfall ­ Teil 2. Spinalisationsphänomene.

Spinal automatisms and reflexes, peripheral neurogenic and myogenic reactions are common in patients with irreversible brain death. They are therefore compatible and are even understood by experienced investigators as confirmation of irreversible brain death. This article provides an overview of the phenomenology of irreversible brain death and discusses it from a neuropathological perspective. Furthermore, irreversible brain death is described in order to distinguish it from pathological movements and motor reactions in comatose patients or patients with disturbed consciousness due to severe brain disorders.

[Irreversible loss of brain function-Part 1: pitfalls in clinical diagnosis]. / Irreversibler Hirnfunktionsausfall ­ Teil 1: Fallstricke der klinischen Diagnostik.

A significant change in the fourth update of the German guidelines on determining brain death is that it includes an explicit profile of requirements on physicians involved in ILBF diagnosis. These requisite qualification criteria have also been formulated due to the fact that, in many hospitals, ILBF diagnosis is only rarely carried out and, as a result, uncertainty frequently arises. Typical difficulties emerge at all stages of ILBF diagnosis, and numerous relevant pitfalls arise that need to be taken into consideration and which might also be relevant in the selection of the method(s) to detect irreversibility. The approaches presented here are suited to achieving a valid result in the evaluation of equivocal ILBF.

[Off-label therapy: current problems from the perspective of the Pharmaceutical Commission of the German Medical Profession]. / Off-Label-Therapie: aktuelle Probleme aus Sicht der Arzneimittelkommission der deutschen Ärzteschaft.

The off-label use of approved pharmaceuticals outside the authorized status is implemented in pharmacotherapy of many diseases, especially for rare diseases and in cases of therapy resistance. The German regulations are presented and analyzed and the relative literature is discussed.

[Long-term treatment of refractory myasthenia gravis with immunoadsorption]. / Langzeitbehandlung der therapierefraktären Myasthenia gravis mittels Immunadsorption.

BACKGROUND AND OBJECTIVE: Myasthenia gravis in the majority of patients is a well treatable neurological autoimmune disorder with a prevalence of 60-150 per million. For the treatment of myasthenic crisis in the intensive care unit the use of therapeutic apheresis, e. g. immunoadsorption or plasma exchange, is well established due to its rapid therapeutic effect, whereas the necessity in long term treatment is still questioned. Aim of this retrospective cohort-study was the assessment of patients with refractory myasthenia gravis in Germany treated by regular immunoadsorption, the characterization of previous therapies and the efficacy of long-term treatment. PATIENT AND METHODS: In total 14 patients (9 women, 5 men, mean age: 40.5 years) were identified in Germany using regular therapeutic apheresis. 13 were treated with different modes of immunoadsorption (10 yen l-tryptophan-adsorption, 2 yen epitope-specific adsorption, 1 yen polyclonal sheep antibody on sepharose) and 1 with plasma exchange. Mean duration of standard treatment of myasthenia gravis before initiation of regular apheresis was 7.8 years. RESULTS: Average duration of analyzed apheresis treatment was 6.4 years, with a mean treatment-interval of 1.1 per week. Mean reduction rate of autoantibodies against acetylcholine-receptor-protein was 50-60 % per session. After initiation of immunoadsorption the mean time of hospitalisation decreased significantly by app. 60 %. In particular the number of myasthenic crises could be reduced by 89 % per year. Tolerability of immunoadsorption was very good, no severe adverse events occurred. CONCLUSION: In conclusion, for the treatment of the subgroup of myasthenia gravis patients becoming refractory to standard treatment immunoadsorption should be regarded as integral part of the therapeutic armamentarium to stabilize and optimize the state of neurologic rehabilitation. This evaluation should be also carefully considered by carriers of health care cost as currently best available evidence to decide on appropriate treatment regimens for these rare patients.

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

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.

Predictors of in-hospital mortality and attributable risks of death after ischemic stroke: the German Stroke Registers Study Group.

BACKGROUND: There is a lack of information about factors associated with in-hospital death and the impact of neurological complications on early outcome for patients with stroke treated in community settings. We investigated predictors for in-hospital mortality and attributable risks of death after ischemic stroke in a pooled analysis of large German stroke registers. METHODS: Stroke patients admitted to hospitals cooperating within the German Stroke Registers Study Group (ADSR) between January 1, 2000, and December 31, 2000, were analyzed. The ADSR is a network of regional stroke registers, combining data from 104 academic and community hospitals throughout Germany. The impact of patients' demographic and clinical characteristics, their comorbid conditions, and the treating hospital expertise in stroke care on in-hospital mortality was analyzed using Cox regression analysis. Attributable risks of death for medical and neurological complications were calculated. RESULTS: A total of 13 440 ischemic stroke patients were included. Overall in-hospital mortality was 4.9%. In women, higher age (P<.001), severity of stroke defined by number of neurological deficits (P<.001), and atrial fibrillation (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.0-1.6) were independent predictors for in-hospital death. In men, diabetes (HR, 1.3; 95% CI, 1.0-1.8) and previous stroke (HR 1.4; 95% CI, 1.0-1.9) had a significant negative impact on early outcome in addition to the factors identified for women. The complication with the highest attributable risk proportion was increased intracranial pressure, accounting for 94% (95% CI, 93.9%-94.1%) of deaths among patients with this complication. Pneumonia was the complication with the highest attributable proportion of death in the entire stroke population, accounting for 31.2% (95% CI, 30.9%-31.5%) of all deaths. More than 50% of all in-hospital deaths were caused by serious medical or neurological complications (54.4%; 95% CI, 54.3%-54.5%). CONCLUSIONS: Substantial differences were found in the impact of comorbid conditions on early outcome for men and women. Programs aiming at an improvement in short-term outcome after stroke should focus especially on a reduction of pneumonia and an early treatment of increased intracranial pressure.

Mini-infarct encephalopathy associated with uncommon microvessel convolute formation presenting with presenile dementia.

A female patient started to suffer from transient ischemic attacks when she was 47 years of age, followed by increasing predominantly left-side spastic tetraparesis, generalized seizures and progressive dementia over a period of 11 years. She died when she was 58 years of age. On gross examination the brain showed enlarged ventricles and arteriosclerotic changes of large extracerebral vessels of the circulus arteriosus. Microscopic examination of the atrophic brain showed innumerable incomplete microinfarcts in the white and gray matter throughout all parts of the brain. In the white matter these lesions were characterized by small foci of demyelination and loss of oligodendrocytes while occasionally some scavenger cells were seen. Axons seemed to be unaffected or displayed irregular axonal regeneratory growth. Any inflammatory reaction failed. In the cerebral cortex and subcortical nuclei the lesions showed loss of neurons and decrease in synaptophysin expression. Intracerebral arteries showed fibrosis or fibrohyalinosis of the entire intracerebral small-vessel network. In addition, numerous uncommon clusters of angioma-like telangiectatic vessels were observed. Medium-sized ischemic infarcts were found in the right putamen and adjacent internal capsule region, left-side dorsolateral brain stem and cerebellar hemisphere as well as a left-side pyramidal tract degeneration. Contralateral pseudohypertrophy of the inferior olivary nucleus was seen. The clinical and the neuropathologic observations made in this patient are compatible with small vessel disease characterized by a multicentric special and not yet described type of incomplete mini-infarcts in cerebral cortex and white matter accompanied by some larger ischemic infarcts of the common type in brain stem and cerebellum.

[Carotid stenting--stratification of the acute phase, indications in secondary prevention from the neurological viewpoint]]. / Carotisstenting--Stratifizierung in der Akutphase, Indikation in der Sekundärprävention aus neurologischer Sicht.

The progress in the technical procedures of stenting in the ICA and the growing expertise in this field need primary multidisciplinary efforts for improving both, indication and periinvasive management of stroke patients. From a neurological point of view in the acute stroke there is an indication on the single case basis, only, e.g. in crescendo-TIA and given TEA-indication but without operability given in the patient. Later on, the stenting should be taken into account only after complex neurovascular workup, incl. CMRT with DWI and PWI, interdisciplinary definitive indication and qualified periinvasive management, i.e., apparative monitoring and neurological examination, e.g., on a stroke unit. Some indications emerge from the present expertise: re-stenosis after TEA, radiogenic stenosis, given indication for TEA, but no operability for technical reasons, e.g. distal ICA-stenosis, or class III or IV risk patients. The contraindications remain to be clarified.

Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.

[Long-term treatment with 7S immunoglobulins in myasthenia gravis. Preliminary clinical results]. / Zur Langzeitbehandlung mit 7S-Immunglobulinen bei Myasthenia gravis. Vorläufige klinische Ergebnisse.

After initial high-dose intravenous 7S immunoglobulin therapy, six patients with seropositive myasthenia gravis received intermittent low-dose 7S immunoglobulins for at least 4-12 months. This treatment was started in five cases following an acute exacerbation of myasthenic symptoms (Oosterhuis class 3-4) and in one case because of marked clinical fluctuations (Oosterhuis class 3). In five of the six patients, there was a clinical response to the immunoglobulin therapy within 2 weeks, followed by marked long-standing improvement and stability of the clinical outcome. In four cases a decrease in the titer of acetylcholine receptor antibodies was noted in parallel. Our observations suggest an additional positive therapeutic effect of long-term, low-dose intravenous immunoglobulin therapy following the acute management of myasthenic exacerbations.

Blunt trauma lesions of the extracranial internal carotid artery in patients with head injury.

Blunt trauma lesions of the extracranial internal carotid artery (ICA) are rare. In our hospital 18 patients with such an injury were diagnosed. All patients were involved in traffic accidents. Most of them had sustained head injuries with fractures of the skull, mandible or maxilla. The onset of neurological signs, most frequently hemiparesis, was usually delayed. 50 percent had bilateral ICA lesions but the clinical presentation was similar to those with unilateral lesions. Mortality of patients with ICA lesions was substantial (28%).

Skeletal muscle antibodies in patients with a thymic tumour but without myasthenia gravis.

Sera from 9 patients with a primary thymic tumour but without myasthenia gravis (MG) at the time of thymectomy were examined for skeletal muscle antibodies. Antibodies to a citric acid extract (CA), associated with the presence of a thymic lymphoepithelioma in MG patients, were detected in 3 sera. AChR antibodies were detected in 5 sera, the concentration markedly elevated in 1 of them. Sarcolemmal and cross-striational antibodies were detected in 2 and 3 sera, respectively. Four of the 5 patients with thymic tumours other than a lymphoepithelioma had AChR antibodies, and 3 of them also had CA antibodies.

Plasma exchange in patients with Guillain-Barré syndrome: clinical improvement in patients with serum IgG antibodies to peripheral nerve tissue.

The mixed hemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange (PE) were examined in 24 patients, 16 patients with acute form and 8 patients with the chronic form of the disease. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after the PE. Before PE antibodies were detected in sera from 15 of the patients. These patients showed clinical improvement during the treatment, however in one of the patients only after a time interval of 2 weeks. After PE, antibodies were detected in sera from only 3 of the patients. The 9 patients without detectable antibodies showed no clinical improvement.

Comprehensive monitoring and computerized tomographic follow up in patients with acute severe head injury: coma-outcome correlations.

In 88 patients with acute severe head injury the Glasgow coma scale (GCS), computerized tomography and autonomic monitoring during the first 24 hours were used to characterize different types of post-traumatic brain dysfunction. A subgroup is defined--GCS 8.1--with signs of diffuse brain swelling and autonomic instability which included two cases with dorsal midbrain lesions. These preliminary results suggest that autonomic instability is a valid criterion for identifying patients suffering from diffuse axonal injury.