Acute interventional recanalisation of vertebrobasilar stenoses by angioplasty: complications and 12 months follow up.

INTRODUCTION: In acute symptomatic vertebrobasilar artery stenosis, the use of mechanical recanalisation remains controversial. The complication rate of acute interventional recanalisation (aIR) has to be considered, as evidence from randomised trials is lacking. In a single centre retrospective case series, we here describe complications and outcome after aIR. METHODS: We retrospectively assessed aIR in a tertiary care centre and included the following parameters: indication for aIR, national institute of health stroke scale (NIHSS) score on admission, recanalisation by thrombolysis in myocardial infarction score (TIMI) grades, post-interventional complications, mortality, NIHSS and modified Rankin scale at follow-up and rate of restenosis. RESULTS: We identified 14 aIR (14 percutaneous transluminal angioplasty with or without stent implantation in 12 patients; 6/12 with thrombolysis; n = 6 vertebral artery, n = 8 basilar artery; 4 women, mean age 67 years). Mortality was 25 % (3/12) after 7 days and 42 % (5/12) after 12 months. In 12/14, interventions are complete (TIMI 3, 86 %), in 2/14, a partial recanalisation (TIMI 2, 14 %) was achieved. In one case, a peri-interventional fatal intracerebral haemorrhage occurred (1/12, 8 %). At late follow-up (mean 342 days), one re-occlusion (1/7, 14 %) and one recurrent stroke (1/12, 8 %) were observed. CONCLUSIONS: In our single centre series of vertebrobasilar aIR recanalisation rate was high. However, procedural safety and clinical outcome varied considerably. The results of aIR need to be assessed in multicentric registers to define the procedural risk and outcome in the clinical setting.

[ALS and frontotemporal dementia - case report and review of the literature]. / ALS und frontotemporale Demenz - Fallbericht und Literaturübersicht.

The occurrence of cognitive decline in amyotrophic lateral sclerosis (ALS), especially in the form of frontotemporal dementia (FTD), has been described previously. Recent molecular biology and histopathology data suggest that both ALS and FTD may share common pathological pathways and may present two phenotypes of the same proteinopathy. The underlying pathophysiological mechanism may be defective RNA- and DNA-modulation, mediated by the proteins TDP43 and FUS. These findings are suggestive of a new disease category of TDP43-proteinopathies, which include ALS, FTD and overlap syndromes. While about half of the FTD cases are associated with TDP43-deposits, tau is found in the other half. A significant clinical overlap to other tauopathies exists here as well, for instance with corticobasal degeneration. In this paper, we present a case report and review the clinical spectrum and current pathogenetic concepts of FTD.

Systemic thrombolysis with rt-PA in patients under 40 years of age: a subgroup analysis of the Cologne Stroke Experience.

BACKGROUND: While the application of intravenous systemic thrombolysis (IVT) with rt-PA (recombinant tissue plasminogen activator) in older patients is currently moving into the focus of epidemiological studies, only few data are available regarding the application in young patients ≤40 years. Single-center data of a thrombolysis register were analyzed with respect to safety and efficacy of the treatment of young patients. METHODS: In a retrospective subgroup analysis of 450 patients treated by IVT within a 3-hour time window, patients ≤40 years were identified (n = 20). Clinical data [age, pretherapeutic stroke severity (National Institute of Health Stroke Scale, NIHSS), OTT (onset to-treatment time), rt-PA-dose, DNT (door[-]to[-]needle time), rate of symptomatic intracranial hemorrhages] and medical history were determined. The clinical outcome was assessed by the mRS (modified Rankin Scale). The results were compared to those of patients >40 years (n = 430). RESULTS: Twenty patients ≤40 years (mean age 32 years) out of 450 patients (4%) were treated by IVT. The percentage of predisposing diseases and vascular risk factors was significantly lower when compared to patients >40 years (p < 0.05). In contrast, the percentage of smokers was significantly higher (55 vs. 24%; p < 0.05). In comparison to patients >40 years, OTT, DNT and NIHSS at admission were not significantly different. After 3 months, 11 of 20 young patients (55%) showed a favorable outcome (mRS 0-1) and 80% were functionally independent (mRS 0-2). In the group of patients >40 years (n = 430), the respective percentages were significantly lower [p < 0.05; 34% (mRS 0-1) and 52% (mRS 0-2), respectively]. Symptomatic intracranial hemorrhages were not observed (in patients >40 years: 4%, p < 0.05). CONCLUSIONS: In comparison to the cohort of patients >40 years, IVT in young patients is safe and leads to a significantly better outcome after 3 months. Our data therefore encourage the use of IVT in young patients.

A giant bilateral calcified chronic subdural hematoma.

BACKGROUND: A calcified chronic subdural hematoma is a rare disease and its neuroradiological presentation is variable. The degree of calcification extends from thin calcified inner membranes to dense calcification and even ossification of the hematoma. Previous reports described a maximum of two hematoma cavities with calcified inner hematoma membranes. METHODS: Neuroimaging report with illustrative computerized tomography images. RESULTS: A patient with a bilateral symptomatic calcified chronic subdural hematoma, or so-called "armoured brain", was admitted to our intensive care unit with clinical signs of increased intracranial pressure. Computerized cranial tomography demonstrated multiple bilaterally located hematoma cavities with thin calcified inner membranes. After neurosurgical intervention by bilateral burr hole trepanation, clinical symptoms improved. CONCLUSIONS: Our case of a calcified chronic subdural hematoma presents with an uncommon imaging pattern with more than four hematoma cavities bounded by predominantly convex- and concave-configured thin calcified inner membranes.

Selective immune adsorption treatment of severe Guillain Barré syndrome in the intensive care unit.

BACKGROUND: The effectiveness of plasma exchange and intravenous application of immunoglobulins (IVIG) for the treatment of the Guillain Barré syndrome (GBS) has been demonstrated in large collectives. In contrast, there are only a few investigations in GBS patients with severe symptoms admitted to the intensive care unit (ICU) and treated with selective immune adsorption (SIA). We compared the efficacy and safety of SIA only versus SIA followed by IVIG in patients with severe GBS. METHODS: Patients with severe GBS admitted to the ICU were treated with SIA only or in combination with IVIG. Severity of symptoms was assessed using Hughes grades and severe GBS was defined as ≥ 3. Data were acquired retrospectively for the last 10 years (1998-2008). RESULTS: Data from 30 GBS patients (age 53 ± 16 years) with severe symptoms (Hughes grade 5: 30% [n = 9], grade 4: 57% [n = 17], grade 3: 13% [n = 4]) were analyzed. The mean Hughes grade at admission was 4.2 ± 0.7. Ten patients were treated by SIA only, 20 patients were treated sequentially with SIA followed by IVIG (30 g/d) over 3 days. The number of SIA sessions was 3.2 ± 0.8. Improvement of Hughes grade 4.2 ± 0.7 to 3.4 ± 0.9 (P < 0.001) occurred within 14.6 ± 15.5 days. Treatment with SIA only was as effective as the sequential therapy with IVIG. The Hughes grade decreased significantly in the group of patients where SIA was performed only (P = 0.008) and in the sequential treatment group (P < 0.001), respectively. In one patient SIA had to be terminated after one session due to ICU complications. Other severe side effects were not observed. CONCLUSIONS: In severely affected GBS patients admitted to ICU treatment with SIA seems to be safe and effective. In comparison to treatment with SIA only, sequential therapy with IVIG was not more effective.

[Cerebrotendinous xanthomatosis]. / Zerebrotendinöse Xanthomatose.

HISTORY AND CLINICAL FINDINGS: A 43-year-old woman had since childhood suffered from progressive dementia. Gait ataxia and mild polyneuropathy were noted in the neurological examination. She also had painful xanthomas of the achilles tendons. A bilateral cataract operation had been performed during adolescence. INVESTIGATIONS: An elevated concentration of cholestanol and a normal cholesterol level were found in the blood samples. The cerebral computed tomography revealed slight cerebral atrophy, predominantly affecting the cerebellum. Neurophysiological tests detected a sensory polyneuropathy in the legs. In addition the electroencephalogram showed a generalized slowing of electrical activity. DIAGNOSIS, TREATMENT AND COURSE: Clinical findings and laboratory values indicated the diagnosis of a cerebrotendinous xanthomatosis. After initiation of a drug therapy, based on a combination of an HMG-CoA-reductase inhibitor (simvastatin 20 mg/day) and a bile acid, chenodeoxycholic acid (15 mg/kg/day), further progression of the disease was prevented. CONCLUSION: The diagnosis of cerebrotendinous xanthomatosis is easily made in patients presenting all clinical symptoms expected in the disease. However, up to 30% of the patients do not show severe xanthomas. Especially in early stages of the disease the diagnosis may be difficult. Treatment can be efficacious and should be started as early as possible to prevent irreversible damage, particularly in the nervous system.

[Erysipel at the lower leg combined with a peripheral peroneus nerve palsy--an unusual occurrence]. / Ein Erysipel am Unterschenkel kombiniert mit einem peripheren Peroneusschaden--Ein seltenes Ereignis.

We present the clinical case of a fifty-year-old man who presented two times with a foot elevator paresis and an erysipel first on the right and after two months on the left side. Afterwards, we carried out a thorough case history with the help of clinical, radiological and magnetic resonance imaging. Even so the clinical pathology of the foot elevator paresis could not be manifested. A compartment syndrome could be discounted. In the context of the second stay during a neurology examination on both legs electromyography was performed and the nerve speed was tested. A peripheral peroneus paresis of unknown level and of unknown aetiology was demonstrated. The erysipel regressed rapidly under intravenous ampicillin antibiotics while the peroneus paresis was unchanged. The patent was released with a peroneus splint on both sides. With this case report we would like to point out the causes of peripheral peroneus paresis with regard to an additional erysipel. This case report is discussed regarding the possible aetiopathology and the current literature.

[Measuring fatigue in patients with multiple sclerosis with standardized methods in German speaking areas]. / Messbarkeit von Fatigue bei multipler Sklerose mithilfe standardisierter Methoden im deutschsprachigen Raum.

Fatigue describes the presence of a pronounced and advanced state of weariness. People with fatigue need more energy and it takes more effort to perform different activities than expected when compared to the patients disability. Fatigue can be observed in up to 92 % of patients suffering from multiple sclerosis. In the presented study, the German fatigue severity scale (dFSS) was established following the English "Fatigue Severity Scale". We enrolled 20 patients suffering from a primary relapsing multiple sclerosis and compared them to 20 healthy controls. Fatigue was detected if at least 4 points were reached in the dFSS. The dFSS demonstrated high validity and reliability. The dFSS is able to differentiate patients with fatigue from healthy controls. As consequence, the dFSS can be used to evaluate fatigue in German speaking individuals. The presented data demonstrated a good internal consistence. The scale is able to measure fatigue in an economic and rapid fashion. Therefore, it can be used in clinical situations for measuring fatigue in German speaking individuals.

Gender change and its impact on the course of multiple sclerosis.

We report the case of a 22-years old genotypic women suffering from a relapsing-remitting multiple sclerosis (MS) according to the Poser criteria. In this patient, a gender change had been performed by androgen-supplementation and surgical intervention. During gender change, the patient experienced further relapses. Different immunomodulatory and immunosuppressive treatment strategies did not stabilise the course of MS in this patient. Actually, an escalating therapy with mitoxantrone has been initiated. During the observation period the patient received long-term testosterone-supplementation. Testosterone levels were elevated in the serum of this genotypic female MS patient under such a hormonal treatment compared to normal ranges before. The clinical course of the patient is presented in this case. As there are several studies investigating an immunomodulatory impact of hormones on the course of MS or experimental allergic encephalomyelitis, we discuss the presented case and a possible influence of androgens in this patient.

[Glycogenesis Type II (M. Pompe). Selective failure of the respiratory musculature--a rare first symptom]. / Glykogenose Typ II (M. Pompe). Selektiver Befall der Atemmuskulatur --Eine seltene Erstmanifestation.

Late-onset Pompe's disease, a generalized lysosomal glycogen storage disease caused by acid maltase deficiency, usually presents as a slowly progressive muscular weakness of proximal muscles in lower limbs, followed by involvement of respiratory muscles. In the case presented here, however, respiratory failure was the first and selective symptom which caused the uncommon appearance of a patient entering our outpatient clinic on foot carrying his own artificial respirator. Intercostal muscle biopsy eventually led to the diagnosis.

[Complications and diagnostic limitations of chronic meningitis]. / Komplikationen und diagnostische Grenzen bei chronischer Meningitis. Eine Kasuistik.

HISTORY AND ADMISSION FINDINGS: A 37-year-old woman was admitted with total loss of vision of the left eye within 24 hours. Additionally, she complained about fatigue, headache, chills, fever, muscle pain and neck stiffness since 4 days. At admission, the body temperature was 38.7 degrees C. Neurological examination revealed papilledema and meningism. INVESTIGATIONS: Ophthalmologic findings were consistent with a papillitis. The vision was lost, the pattern-shift checkerboard visual evoked potentials were not measurable. MRI of the brain and the optical nerve was without pathological findings, meningeal or cerebral Gadolinium enhancement was not present. The CSF analysis yielded a lymphocytic meningitis with 249 cells/mm (3), the glucose ratio of cerebrospinal fluid and serum was normal. DIAGNOSIS, TREATMENT AND COURSE: The papillitis was treated unsuccessfully with high-dose methylprednisolone, the left eye remained blind. Persistence of the pleocytosis under initial treatment with aciclovir and ceftriaxone, reduction of the glucose ratio of cerebrospinal fluid and serum and intrathecal immunoglobuline A -- synthesis required a change of the diagnostic and therapeutic regimen. Various common and rare differential diagnoses were considered and ruled out, a chronic meningitis of unclear aetiology with the complication of amaurosis was diagnosed. In consideration of the most probable diagnosis, a tuberculostatic therapy was initiated. A prolonged reduction of the pleocytosis and normalization of cerebrospinal fluid parameters could be observed. CONCLUSIONS: A large number of aetiologies can cause chronic meningitis; this case report reviews the most important differential diagnoses and highlights the limitations of the diagnostic work-up although various methods are available. Clinical course and symptoms of chronic meningitis are mild to moderate and may even be absent, but it can cause severe complications.

Long-term persisting interferon beta-1b neutralizing antibodies after discontinuation of treatment.

OBJECTIVES: Neutralizing antibodies (NAB) against interferon beta (IFNB) with presumably negative impact on treatment outcome have been described in up to 42% of patients undergoing IFNB treatment. However, in most cases NAB decrease despite continuation of IFNB therapy. Observations on NAB after discontinuation of IFNB therapy are lacking. Here, we report for the first time on NAB which now persist for several years following discontinuation of IFNB treatment. MATERIALS AND METHODS: We present two multiple sclerosis patients followed over 8 and 10 years. NAB have been measured repeatedly and are presented together with clinical data. NAB developed after 2 years of treatment and persisted despite discontinuation of treatment at high titers for more than 4 years. CONCLUSION: Our data indicate that IFNB therapy may induce long-term NAB production which persists even after discontinuating IFNB treatment. Possible immunological mechanisms are discussed.

Early antithrombotic prophylaxis with low molecular weight heparin in neurosurgery.

BACKGROUND: Despite the high risk of venous thromboembolic events (VTE) in neuro-surgical patients, heparin prophylaxis has not been routinely established due to concern about bleeding complications. After initiating early low molecular weight heparin (LMWH) prophylaxis, we reviewed our patients in order to examine the viability of this practice. METHOD: Over a 3 year period, the records of patients admitted for elective neuro-surgery (ES), head injury (HI) or spontaneous intracranial haemorrhage (ICH) were analysed. Prophylaxis was performed with certoparin (3000 U anti-factor Xa s.c.) on the evening before ES and within 24 hours after surgery or admission whenever a CT did not show a progressive haematoma. Contraindications for LMWH were prothrombin time <70%, partial thrombo-plastin time >40 s, platelet count <100.000/ml, and platelet aggregation test sum <60%. The incidence of bleeding complications, VTE, and resulting morbidity/mortality was assessed. FINDINGS: 294 patients were admitted for ES, 344 for HI, and 302 for ICH. 155 of these were excluded because of contraindications. Intracranial bleeding was recorded in 1.5% (ES 1.1%, HI 3.5%, ICH 0%) and operative revision was performed in 1.1% (ES 0.7%, HI 2.8%) of patients. One case of moderate disability and no mortality occurred. The incidence of VTE and pulmonary embolism was documented in 0.2% and 0.1% of patients, with no associated mortality. No heparin induced thrombocytopenia was observed. INTERPRETATION: In neurosurgical patients, antithrombotic prophylaxis with certoparin was determined to be safe and efficacious when contraindications are carefully considered and a 12-hour time interval before and after surgery was guaranteed. This retrospective analysis should encourage a prospective trial of early LMWH prophylaxis.

[The diagnosis of brain death: medical and legal aspects with special reference to the German Transplantation Law (TPG)]. / Die Diagnose des Hirntodes: Medizinische und juristische Aspekte unter Berücksichtigung des Transplantationsgesetzes (TPG) der BRD.

The diagnosis of brain death following total and irreversible cessation of all cerebral functions is based on anthropological assumptions and conventions as well as on the exact medical diagnosis of total loss of brain function. The question whether individual life ends after cerebral function is irreversibly lost cannot be answered by medical definition alone. Clear and unrefutable legal definitions of death and the cessation of the rights of the individual must be provided before organs may be harvested from brain dead individuals. Acceptance of these definitions by the general population is of paramount importance for the practice of organ donation. In the first part of this article, the legal definition of death and the provisions of the German transplantation law are critically reviewed. The legal statements deal with the question of the definition of death and how death can be detected. The provisions of the German transplantation law are referenced with special attention to the provision of prior consent to the removal of organs following after the diagnosis of brain death. The provisions of the German constitution with respect to the preservation of the personal rights of the individual are discussed in the light of organ harvesting. The second part deals with the medical procedure of determining brain death in adults. The medical statements pertain to the diagnostic steps to be taken in the diagnosis and determination of brain death. The prerequisites for entering the diagnostic procedure to determine brain death are described. The clinical signs of total and irreversible cessation of brain function are listed, and the technical examinations to corroborate the clinical signs of brain death as accepted in Germany are delineated. In the perspective of the authors, individuals having suffered brain death still possess the protection of their personal human rights according to the German constitution since it cannot be conclusively demonstrated that total loss of brain function alone constitutes the cessation of life in the sense of the German constitution.

[Transient neonatal myasthenia gravis]. / Transiente neonatale Myasthenia gravis.

Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.

Bell's palsy: electrodiagnostics are not indicative of cerebrospinal fluid abnormalities.

Electrodiagnostic testing (electromyography, electroneuronography, and blink reflex) and cerebrospinal fluid (CSF) examination (cell count, immunoglobulins, and antigen-specific intrathecal immunoglobulin G synthesis against herpes simplex virus, varicella zoster virus, cytomegalovirus, and Borrelia burgdorferi sensu latu) were performed in 56 patients with Bell's palsy. The CSF was normal in 45 patients and abnormal in 11 patients. Acute borreliosis was the most common specific pathological CSF finding (4 of 11). Electromyography revealed abolished volitional activity in 22% of patients with normal CSF and in 36% with pathological CSF. Electroneuronographic tests with an amplitude decrease of more than 90% on the affected side or abolished responses were found in 20% of patients with normal CSF and in 18% with pathological CSF. Abolished orbicularis oculi reflexes were seen in 67% of patients with normal CSF and in 82% with pathological CSF Concerning electrodiagnostic testing, no statistically significant difference between patients with normal and abnormal CSF was found, so we conclude that electrodiagnostic testing has no indicative value for abnormal CSF in Bell's palsy.

Recent advances of therapeutic apheresis in Guillain-Barré syndrome.

Acute idiopathic demyelinating polyneuritis (AIDP), commonly known as the Guillain-Barré syndrome (GBS), is an immune-mediated demyelinating disease of the peripheral nerve and nerve roots. A number of immunological mechanisms were described, but the exact pathomechanism has not been explained fully. Presumably, a variety of immunological processes lead to a relatively uniform clinical phenotype. Two large multicenter studies showed that plasma exchange (PE) was significantly superior to supportive treatment only. Selective adsorption (SA) also was employed as a method of therapeutic apheresis, and various smaller studies established that both PE and SA are equally effective treatments for GBS. Recently, it was demonstrated that the number of apheresis treatments should be adapted to the severity of disease. A large multicenter controlled study established equal efficacy of PE and intravenous immunoglobulin treatment (IVIg) as well as the combination of PE and IVIg. Since that time, the use of apheresis for the treatment of GBS declined in many countries due to the easier application of IVIg. The number of patients treated in larger hospitals with long-standing experience in the treatment of GBS also has declined.

Serial evoked potentials and outcome in cerebrovascular critical care patients.

Median-nerve evoked somatosensory evoked potentials (SEPs) and brainstem auditory evoked potentials (BAEPs), examined early in the course of patients suffering from cerebrovascular disease, correlate statistically significantly with outcome. Little is known about the changes of evoked potentials in the course of disease and their correlation to outcome. In a series of 215 patients (75 supratentorial infarctions, 36 infratentorial infarctions, 58 supratentorial hemorrhages, 18 infratentorial hemorrhages, and 28 aneurysmatic subarachnoid hemorrhages) requiring neurologic intensive care treatment, we prospectively examined the correlation between the findings of serial SEPs and BAEPs and outcome at 4 weeks. Evoked potentials were examined after admission, after 1 week, and after 2 weeks. The findings were classified in 4 categories (normal, unilateral or bilateral pathologic findings, unilaterally attenuated, and bilaterally attenuated). Clinical outcome was determined by classification according to the Glasgow Outcome Scale (death, persistent vegetative state, severely incapacitated, mildly incapacitated, and recovery). Statistical evaluation was performed using Fisher's exact test for all variables. In all subgroups, SEPs correlated statistically significantly with outcome at all three examinations. No correlation was found for BAEPs at first examination in infratentorial disease, nor at second examination in subarachnoid hemorrhages. In all other cases, SEPs and BAEPs were correlated statistically significantly with outcome at all three examination timepoints.

Immunoadsorption in Guillain-Barré syndrome and myasthenia gravis.

Elimination of circulating antibodies by hemapheresis is an empirical treatment concept in various neuroimmunological diseases. Plasma exchange (PE) has been shown to be superior to symptomatic treatment in Guillain-Barré syndrome (GBS) in two large multicenter studies. It is also effective in myasthenia gravis (MG), although no comparative studies have been performed. Immunoadsorption (IA) using polyvinyl alcohol gel columns to which phenylalanin (IM-PH) or tryptophan (IM-TR) are covalently bound is an alternative to PE, and seems to have equal efficacy and comparable side effects. This method also obviates the need for replacement of plasma with human albumin or plasma. We compared the treatment results of 11 patients with GBS treated by PE to those of 13 patients treated by IA using an IM-TR column. Here, we found no statistically significant differences with regard to efficacy and clinical or procedural complications. From these data we conclude that immunoadsorption can be used as an equal alternative to PE. A large multicenter study comparing PE, intravenous immunoglobulins (IVIG), and the combination of both in the treatment of GBS revealed no significant difference between the 3 treatment groups. In MG, only 2 small studies have been performed using IA, and no studies comparing PE or other treatments to IA have been conducted. Both investigations of IA therapy demonstrated a marked reduction in the acetylcholine receptor (AchR) antibodies and a sustained improvement of the clinical signs. These results therefore show that IA is an effective treatment for myasthenia gravis.