Behavioural changes in patients with intellectual disability treated with brivaracetam.

OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of brivaracetam (BRV) in residential patients at our epilepsy centre. PATIENTS AND METHODS: We assessed retrospectively 33 patients (14 females; mean age 38.2 years, with range 17-63 years) with intellectual disability (ID) and drug-resistant epilepsy using an industry-independent, non-interventional study design based on standardized daily seizure records. Mean seizure frequency was compared between the 3-month baseline period and subsequent 3-month treatment period. Evaluation, including calculation of retention rate, was carried out for the intervals 3-6 and 9-12 months after brivaracetam initiation. Responders were defined as having a 50% reduction in seizure frequency. The Clinical Global Impression scale (CGI) was applied to allow assessment of qualitative changes in seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights into challenging behaviour. RESULTS: The responder rate was 19%, and one non-responder attained an improvement in CGI score. The retention rate after 12 months was 37%. Brivaracetam treatment was stopped because of adverse events (n = 3), lack of efficacy (n = 8) or both (n = 6). Thirteen patients experienced behavioural changes, with aggressive behaviour being the commonest effect. We also observed ataxia (n = 2), gastrointestinal disorder (n = 3) and sedation (n = 2). The ABS showed deterioration, or new occurrence, of aggressive behaviour in 13 patients. CONCLUSIONS: Brivaracetam seems to be effective in a small number of patients suffering from difficult-to-treat epilepsy and intellectual disability. Challenging behaviour was documented in a relevant number of patients, with psychiatric illness being a risk factor for this.

Behavioural changes in patients with intellectual disability treated with perampanel.

OBJECTIVES: The aim of this cross-sectional retrospective study was to assess the tolerability and efficacy of perampanel in patients with drug-resistant epilepsy who also suffered from intellectual disability (ID). PATIENTS AND METHODS: We used an industry-independent, non-interventional retrospective evaluation based on standardized, daily seizure records. Twenty-seven patients with ID and drug-resistant epilepsy were started on perampanel between September 2012 and November 2015 after a 3-month observation period without perampanel treatment. Perampanel was given at a maximum dosage of 4-12 mg daily. Evaluation was carried out after 6, 12 and 24 months, including calculation of the retention rate. Mean seizure frequency was compared between the 3-month baseline period and subsequent 3-month treatment periods. The Clinical Global Impression scale was applied to assess qualitative changes in seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights into challenging behaviour. RESULTS: Perampanel was efficacious and well tolerated in five of 25 patients. In 18 patients, perampanel treatment was stopped, mainly because of adverse events (n=6), lack of efficacy (n=3) or both (n=9). Behavioural changes were documented in 15 of 27 patients, with aggressive behaviour being the commonest effect; we observed ataxia (n=6) and sedation (n=8) in further patients. The ABS showed worsening of aggressive behaviour in six patients. CONCLUSIONS: Perampanel was well tolerated and efficacious in one-fifth of our patients. We observed challenging behaviour, ataxia and sedation in a relevant number of patients with ID under perampanel treatment. Further studies are warranted to explore the tolerability of perampanel in patients with ID.

[Guidelines for Non-Invasive and Invasive Home Mechanical Ventilation for Treatment of Chronic Respiratory Failure - Update 2017]. / S2k-Leitlinie: Nichtinvasive und invasive Beatmung als Therapie der chronischen respiratorischen Insuffizienz ­ Revision 2017.

Today, invasive and non-invasive home mechanical ventilation have become a well-established treatment option. Consequently, in 2010 the German Society of Pneumology and Mechanical Ventilation (DGP) has leadingly published the guidelines on "Non-Invasive and Invasive Mechanical Ventilation for Treatment of Chronic Respiratory Failure". However, continuing technical evolutions, new scientific insights, and health care developments require an extensive revision of the guidelines.For this reason, the updated guidelines are now published. Thereby, the existing chapters, namely technical issues, organizational structures in Germany, qualification criteria, disease specific recommendations including special features in pediatrics as well as ethical aspects and palliative care, have been updated according to the current literature and the health care developments in Germany. New chapters added to the guidelines include the topics of home mechanical ventilation in paraplegic patients and in those with failure of prolonged weaning.In the current guidelines different societies as well as professional and expert associations have been involved when compared to the 2010 guidelines. Importantly, disease-specific aspects are now covered by the German Interdisciplinary Society of Home Mechanical Ventilation (DIGAB). In addition, societies and associations directly involved in the care of patients receiving home mechanical ventilation have been included in the current process. Importantly, associations responsible for decisions on costs in the health care system and patient organizations have now been involved.The currently updated guidelines are valid for the next three years, following their first online publication on the home page of the Association of the Scientific Medical Societies in German (AWMF) in the beginning of July 2017. A subsequent revision of the guidelines remains the aim for the future.

[Epilepsy and transverse sternum fractures: sternum fractures in drug-induced osteopenia]. / Sternumfraktur bei medikamenteninduzierter Osteopenie: Epilepsie und Sternumquerfraktur.

Fractures of the sternum are a very rare injury. The combination of indirect trauma and transverse fracture in case of an epileptic seizure has been described only in one case. A sternal fracture in a 32-year-old woman was treated by plate osteosynthesis because of progressive pain. In the current literature, there are no clear recommendations for the treatment of such fractures. Plate osteosynthesis, as an alternative to conservative treatment of such fractures, is presented and discussed.

[Botulinum toxin in the treatment of adult spasticity. An interdisciplinary German 10-point consensus 2010]. / Botulinum-Neurotoxin in der Behandlung der Spastizität im Erwachsenenalter. Ein interdisziplinärer deutscher 10-Punkte-Konsensus 2010.

Spasticity is one of the major causes of functional impairment in adults with lesions of the central nervous system. For instance, approximately 30% of post-stroke patients suffer from different degrees of spasticity with possible consecutive impairments. Numerous studies or meta-analyses showed that local injections of botulinum toxin in spastic muscles lead to dose-dependent reduction in muscle tone and improvement of passive movements (e. g. facilitated care), especially following repeated injections.However, country-specific regulations and patient-remote administration in German health care often do not allow adequate provision of this therapy. Thus, the present consensus statement based on the EBM analyses of the published international literature tries to highlight recent advances and the standard in the field of local spasticity treatment, aiming to facilitate communication between the decision makers and German reimbursement institutions in health care. Prior to initiation of BoNT-A injections, patient-oriented goals should be identified in a multiprofessional context to assure realistic goals for this specific treatment and patient expectations. In Germany for the treatment of focal spasticity following stroke three products have been approved: Botox® (Pharm Allergan, Ettlingen), Dysport® (Ipsen Pharma, Ettlingen) and Xeomin® (Merz Pharma, Frankfurt/Main). For all preparations safety has been repeatedly shown. Functional improvements have also been illustrated for selected patients concerning hand/arm function and gait. The dose per muscle and the selection of muscles to be injected have to be individualized according to the patient's symptoms and should be accompanied by modern neurorehabilitative therapies such as redression or repetitive activation of the injected and antagonistic muscles.

[Non-invasive and invasive mechanical ventilation for treatment of chronic respiratory failure. S2-Guidelines published by the German Medical Association of Pneumology and Ventilatory Support]. / Nichtinvasive und invasive Beatmung als Therapie der chronischen respiratorischen Insuffizienz. S2-Leitlinie herausgegeben von der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

The field of mechanical ventilation is highly important in pulmonary medicine. The German Medical Association of Pneumology and Ventilatory Support ["Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP)"] therefore has formulated these guidelines for home mechanical non-invasive and invasive ventilation. Non-invasive home mechanical ventilation can be administered using various facial masks; invasive home mechanical ventilation is performed via a tracheostomy. Home mechanical ventilation is widely and increasingly accepted as a treatment option for chronic ventilatory failure which most often occurs in COPD, restrictive lung diseases, obesity-hypoventilation syndrome and neuromuscular disorders. Essential for the initiation of home mechanical ventilation are the presence of symptoms of ventilatory failure and the detection of hypoventilation, most importantly hypercapnia. These guidelines comprise general indication criteria along with disease-specific criteria summarised by treatment algorithms. In addition, the management of bronchial secretions and care of paediatric patients are addressed. Home mechanical ventilation must be organised around a specialised respiratory care centre with expertise in patient selection, the initiation and the control of home mechanical ventilation. In this regard, the guidelines provide detailed information about technical requirements (equipment), control and settings of mechanical ventilation as well as organisation of patient care. A key requirement for home mechanical ventilation is the qualification of specialised home-care services, which is addressed in detail. Independent living and the quality of respiratory care are of highest priority in patients receiving home mechanical ventilation, since home mechanical ventilation can interfere with the integrity of a patient and often marks a life-sustaining therapy. Home mechanical ventilation has been shown to improve health-related quality of life of patients with chronic ventilatory failure. Long-term survival is improved in most patient groups, even though the long-term prognosis is often severely limited. For this reason, ethical issues regarding patient education, communication with ventilated patients at the end of life, living will, testament and medical care during the dying process are discussed.

Gasperini syndrome as clinical manifestation of pontine demyelination.

The Gasperini syndrome is a very rare brainstem disease characterized by the typical combination of ipsilateral lesions of the cranial nerves V-VII and dissociated contralateral hemihypesthesia, whereas both contralateral and ipsilateral hypacusis was described. Since the first description in 1912, only a few cases of this crossed brainstem syndrome were published so far. Pontine infarction and bleedings were the reported causes of the syndrome. Here we report a 44-year-old man with the classical Gasperini syndrome due to pontine demyelination in multiple sclerosis. The clinical findings were correlated with changes on MRI. The present case shows that classical crossed brainstem syndromes are topological terms not invariably associated with brainstem ischemia in particular vascular areas and may contribute to the differential diagnosis of peripheral facial nerve palsy.

Molecular diagnosis of German patients with late-onset glycogen storage disease type II.

UNLABELLED: In patients with late-onset glycogen storage disease type II, one mutation, c.-32-13T>G, in the α-glucosidase (GAA) gene is identified frequently in European populations from different regions along with many rarer mutations. We have performed molecular genetic investigations in 18 German index patients with late-onset disease. The c.-32-13T>G, c.525delT (p.Glu176fsX45), and c.2481+102_2646+31del mutations were detected by PCR/restriction enzyme digest. Other mutations were detected by sequencing. All patients were compound heterozygous and 17 patients harboured the c.-32-13T>G mutation. Seven other previously described mutations (including the c.-32-13T>G) were identified, of which the p.C103G (c.307T>G) and the c.2481+102_2646+31del mutations were present each in three unrelated patients. Sequencing revealed five novel mutations. CONCLUSIONS: Genetic testing was able to identify the genetic defects in all patients and screening of the c.-32-13T>G mutation identified 94% of the cases. This is important for quick and reliable diagnosis, especially in view of enzyme replacement. Among the rarer mutations, c.2481+102_2646+31del and p.C103G are rather frequent in Germany.

[Treatment of sialorrhea in patients under long-term ventilation]. / Behandlung der Sialorrhoe bei beatmeten Patienten.

Sialorrhea (drooling or excessive salivation) is a common problem in patients with progressive neurolomuscular diseases and bulbar palsy. Contributing factors are hypersecretion of saliva induced by cholinergic drugs and poor dental status. Non-invasive ventilation is often severely impaired in these patients. Treatment should be initiated with a thorough evaluation of the medication and of the oral status by an otorhinolaryngologist. As drooling is commonly caused by poor oral or pharyngeal neuromuscular control, swallowing therapy should be initiated by a speech therapist. Further treatment options are anticholinergic medications, botulinum toxin injections into the salivary gland, radiation and and surgical procedures. Whereas systemic anticholinergic medications lead often to side effects, the (ultrasound-guided) injection of botulinum toxin into the parotid and submandibular gland is a safe and effective method for controlling drooling for at least 2 months.

[Basic principles of non-respiratory physiotherapy for neuromuscular diseases]. / Grundlagen der nichtrespiratorischen Physiotherapie bei neuromuskulären Erkrankungen.

Loss of function, muscle pain and secondary muscoloskeletal complaints are common symptoms of patients with neuromuscular disease. Many patients develop a progressive handicap. Physiotherapeutic treatment is often used in the management of neuromuscular diseases. Different therapeutic strategies are useful depending on the stage and pathophysiology of the disease and with regard to the extent of the patient's handicap. The aims of the physiotherapy and realistic targets should be discussed critically with the patient at the beginning of the treatment. We propose different physiotherapeutic strategies depending on the stage of the underlying disease: 1) Patient is able to walk--active phase: education in self-training with regard to the risks of exhaustion. Manual and physical treatment of mycofascial complaints. 2) Progressive functional loss--assistive phase: support of compensation and daily functioning. 3) Patient in wheelchair or bedbound, loss of most voluntary functions--passive phase. The knowledge of the pathopysiology of the underlying disease is essential for the development of therapeutic strategies. Loss of upper neurons leads to the development of spasticity and muscle hypertonia whereas muscular atrophy and weakness is a prominent feature of lower motor neuron loss. Overtreatment and exhaustive training may lead to secondary muscle damage in primary myopathies. Training in short sessions with intervals between may have protective effects.

[Technical aspects of mechanical insufflator-exsufflators. Construction and function of the Emerson CoughAssist]. / Technische Aspekte mechanischer Hustenhilfen. Aufbau und Funktion des Emerson CoughAssist.

The electromechanical insufflator-exsufflator (Emerson CoughAssist) was developed as an aid for patients with neuromuscular disorders suffering from impaired cough. The insufflator-exsufflator simulates and supports physiological cough by supporting inspiration with positive pressure and shifting this positive pressure rapidly into a negative pressure that supports exsufflation and thus bronchial clearance. Maximum pressures are +/- 60 cm H2O, pressures between 30 and 50 cm H2O are sufficient to produce assisted cough in adults with neuromuscular disease. The pressure shift from positive to negative occurs with 0.02 sec and is regulated by a magnetic valve. An anaesthetic facemask is used as interface, alternatively, a mouthpiece can be used in combination with a nose strap. It is also possible to use the insufflator-exsufflator in patients with tracheostomy. We present in this article detailed information about the technical principles and practical use of the electromechanical insufflator-exsufflator.

Iatrogenic (para-) spinal abscesses and meningitis following injection therapy for low back pain.

Low back pain is often treated with paraspinal injections of analgesics and steroids. Infectious complications of these techniques are rare but they can potentially hold high risks for the patients. History and clinical data of all patients admitted to a neurological unit suffering from community acquired purulent meningitis were prospectively analyzed during an 8 year interval (1992 and 2000) with special regard to the previous medical history. One hundred and twenty eight patients were included in the study. Eight out of 128 patients (6.25%) had a history of single or repeated paravertebral (4/8), facet-joint (2/8), peridural (1/8) or spinal (1/8) injections 2-21 days before admission to the hospital. In six out of eight patients either Staphylococcus aureus (4/8) or coagulase-negative staphylococci (2/8) were found in the cerebro spinal fluid (CSF), in two patients no causative organism was detected. One patient died, three survived with sequel. Repeated paraspinal, peridural or spinal injections with analgesic drugs in combination with corticosteroids hold a risk for parameningeal inoculation of bacteria resulting in paraspinal, spinal, and epidural abscesses or meningitis. The absolute frequency of these complications may be rare but they are responsible for a considerable proportion of community acquired purulent CNS infections.

Excess glutamate levels in the cerebrospinal fluid predict clinical outcome of bacterial meningitis.

BACKGROUND: The clinical course of bacterial meningitis still is characterized by a high mortality and frequent neurological deficits in survivors. In addition to other potentially neurotoxic mediators of inflammation, the excitatory amino acid glutamate, which has been implicated in neuronal death in a variety of other neurological diseases, may also be involved in the pathological process of bacterial meningitis. OBJECTIVES: To investigate the prognostic value of the glutamate concentration in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. PATIENTS AND METHODS: Thirty consecutive patients with bacterial meningitis were included in a prospective study. The clinical severity of the disease was assessed on admission and 14 days after the beginning of antibiotic treatment by means of the Glasgow Coma Scale. Studies of CSF were performed on admission and after 3 to 6 days. In addition to standard CSF investigations, including cell count, cytologic findings, protein analysis, glucose and lactate levels, and microbiological tests, the concentration of glutamate in the CSF was measured by an enzymatic assay. RESULTS: At admission, both CSF cell count and concentration of glutamate correlated well with the severity of the disease. After treatment, glutamate concentrations decreased significantly to normal or only slightly elevated levels in 23 patients. However, in 7 patients glutamate levels remained markedly increased. In this group, clinical outcome was significantly worse than in the group of patients with low glutamate levels in the second CSF analysis. CONCLUSIONS: A prolonged increase of glutamate levels in the CSF may predict poor clinical outcome in patients with bacterial meningitis, possibly because of the sustained neurotoxic effects of this excitatory neurotransmitter.

Stroke following variceal sclerotherapy.

OBJECTIVE: Paradoxical embolism via a patent foramen ovale (PFO) has been identified as a potential risk factor for ischaemic stroke. Such occurrences are associated with risk factors for deep vein thrombosis (DVT), e. g. pregnancy, immobilisation, and surgery of the lower limbs. OBSERVATION: A 54-year-old otherwise healthy female presented with acute onset motoric aphasia and brachiofacial right hemiparesis. The cranial computed tomography showed a left striatal ischaemic infarction. The patient's history revealed a variceal sclerotherapy with polydocanol 0,5% three days prior to the onset of symptoms. Echovist TCM doppler revealed a right-to-left shunt. A patent foramen ovale (PFO) was detected by transesophageal echocardiography. There was no evidence of DVT in bilateral lower-extremity venous duplex ultrasound scanning. Other potential risk factors of stroke including thrombophilia could not be identified. The patient was treated with a high dose regimen of heparin and a further anticoagulation treatment was recommended. CONCLUSION: This case suggests a probable causal relationship between variceal sclerotherapy and paradoxical embolism resulting in a stroke. Variceal sclerotherapy might be a potential, but rare risk of embolism.

Transcutaneous and intra-arterial blood gas monitoring--a comparison during apnoea testing for the determination of brain death.

Intra-arterial (i.a.) and transcutaneous (t.c.) blood gas monitoring were compared with in vitro blood gas analysis (abg) during apnoea testing for the determination of brain death in a prospective observational study. All three methods were used simultaneously in 19 patients in whom brain death was suspected. Brain death was confirmed in each case adhering to the recommendations of the Scientific Advisory Board of the German Federal Chamber of Physicians which demand a PCO2 of at least 60 mmHg. In vitro parameters ranged from 23.2 to 80.4 mmHg (PCO2), 52.7 to 509.9 mmHg (PO2), and 7.072 to 7.591 (pH). The intra-individual correlations between both monitoring methods (rPCO2=0.958, rPO2=0.859) and between each of them and abg (r>0.960) were high. Absolute deviations from abg for the corrected as well as uncorrected measurements were similar for both methods, except with regard to group bias where an advantage for the i.a. values emerged. Since many of the i.a. measurements failed and the disposable i.a. probes cost much more than the t.c. electrodes, the i.a. technique at present holds no advantage over t.c. measurements in testing for apnoea in suspected brain death except where simultaneous monitoring of pH and temperature are desired.

[Managing life and death wishes of invasively ventilated amyotrophic lateral sclerosis patients]. / Der Umgang mit Lebens- und Todeswünschen bei invasiv beatmeten ALS-Patienten.

BACKGROUND: Find of life decisions of patients with amyotrophic lateral sclerosis and respiratory failure are influenced by several environmental factors. PATIENTS AND METHODS: We describe the course of disease and decision making of four of these patients. RESULTS: Most decisions have been inconsistent and were seen to be depending on actual situations. Main factors were: 1. preclinically (before respiratory failure) medical information, 2. during respirator dependency in the hospital's intensive care unit the clinical setting and the individual perspective depending on the patient's private situation, 3. at home ventilation the family's situation and conflicts. Especially the patients requests for disconnection from the respirator overtaxed their carers capacities. CONCLUSION: We conclude that there is need for professional psychosocial intervention for the patients and their families.

[Brain syndrome and home ventilation--diagnosis, therapy and consequences]. / Hirnorganisches Psychosyndrom und Heimbeatmung--Problematik, Diagnose und Therapie.

BACKGROUND: A growing number of patients with neuromuscular diseases has been treated with mechanical ventilatory support during the last years. In some of these patients acute or chronic organic brain syndromes complicate the situation. PATIENTS AND METHODS: We present case reports of 5 patients who have been ventilated at home with neuromuscular diseases but who also suffered from brain syndromes of different etiology. CASE REPORTS: (1) Multifactorial acute organic brain syndrome after intensive care therapy. (2) Recurrent paranoid psychosis correlating with hypercapnia. (3) Oneiroids (awake dreamings). (4) Refusal of the rejection of mechanical ventilation facing dyspnea. (5) Persistent vegetative state after polyradiculomyeloencephalitis. DISCUSSION: Patients with hypoventilation or mechanical ventilation often present with various types of brain syndromes. Careful history taking and the use of laboratory and imaging techniques allow the differentiation in primary and secondary (metabolic) brain syndromes. With respect to the fact that home ventilation has marked consequences for the patient and his carer organic disorders of brain function raise two questions: (1) Is the patient able to understand and critically reflect the consequences of long-term mechanical ventilation? (2) Is the patient able to understand and manage the practical aspects and skills of home-ventilation. e.g., does he have the mental capacity for a sufficient compliance? From our point of view patients with severe brain syndromes should not be selected for home-ventilation.