Optimizing home-based long-term intensive care for neurological patients with neurorehabilitation outreach teams - protocol of a multicenter, parallel-group randomized controlled trial (OptiNIV-Study).

BACKGROUND: Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN. METHODS: This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition. DISCUSSION: The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER. TRIAL REGISTRATION: The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 .

Cycle ergometer training vs resistance training in ICU-acquired weakness.

OBJECTIVES: We investigated the effectiveness of cycle ergometer training and resistance training to enhance the efficiency of standard care to improve walking ability, muscular strength of the lower limbs, cardiovascular endurance and health-related quality of life during inpatient rehabilitation in intensive care unit acquired weakness. MATERIALS & METHODS: Thirty-nine patients with severe to moderate walking disability were enrolled in one of the three experimental groups: (a) ergometer training group, (b) resistance training group and (c) control group (standard care only). Intervention was applied 5 days a week over a 4-week period during inpatient neurological rehabilitation. We evaluated walking ability (Functional Ambulation Category test, timed up and go test, 10-metre walk test and 6-minute walk test), muscle strength (Medical Research Council and maximum muscle strength tests), cardiovascular endurance and muscular endurance of the lower limbs at the fatigue threshold (physical working capacity at fatigue threshold) and quality of life (medical outcomes study SF-36 form). All tests were performed at baseline, after two weeks of treatment and at the end of the 4-week intervention period. RESULTS: Ergometer training and resistance training enhanced the effectiveness of standard care in order to improve (a) lower limb muscle strength, (b) walking ability and (c) cardiorespiratory fitness during inpatient rehabilitation of intensive care acquired weakness. In addition, ergometer training may be superior to resistance training. CONCLUSIONS: Our data encourage more research to develop and implement these training tools in rehabilitation programmes for intensive care acquired weakness.

Histological characterization and biochemical analysis of paraspinal muscles in neuromuscularly healthy subjects.

INTRODUCTION: There are no generally accepted histopathological reference values in paraspinal skeletal muscle biopsies. METHODS: We examined multifidii muscle biopsies from 20 neuromuscularly healthy subjects using routine histological stains and biochemical analyses of respiratory chain enzymes. RESULTS: Staining showed incomplete myopathic features, such as increased variability in fiber size, type 1 hypertrophy, rounded fiber shape, endomysial fibrosis, and replacement by adipose tissue. Acid phosphatase reaction was positive in up to 35% of the selected muscle fibers. Mitochondrial changes were obvious but revealed no selective age dependence. Reduced complex I, cytochrome c oxidase (COX), and citrate synthase (CS) could be observed. CONCLUSIONS: Because the increased variability in morphological details can easily be misinterpreted as myopathic changes, analysis of paraspinal muscles should take into consideration that incomplete myopathic features and reduced oxidative enzyme activities for complex I, COX, and CS are normal variations at this location.

Myositis associated with localized lipodystrophy: an unrecognized condition?

Lipodystrophies represent a heterogeneous group of diseases characterized by altered body fat repartition and often metabolic alterations. Here we illustrate a 20 year old male with myositis in association with localized lipodystrophy. Immunohistochemical stainings revealed a regular pattern of dystrophin, dysferlin, sarcoglycans, and theletonin. Furtermore, there was no evidence of Lamin A/C deficiency. A nearly identical clinical and histological picture has been described in three patients up to now. Although it is difficult to speculate on a causative pathophysiological mechanism at this time, it is possible that this association represents an unrecognized condition.

The combination of dopa-responsive parkinsonian syndrome and motor neuron disease.

BACKGROUND: Idiopathic Parkinson's syndrome (IPS) and motor neuron disorders (MND) are generally considered as distinct clinicopathological entities. However, cooccurrence of different neurodegenerative disorders is more frequent than would be expected. Therefore, there is an ongoing discussion whether some entities represent parts of a common spectrum. OBJECTIVE AND METHODS: We describe clinical hallmarks and treatment options in a group of 8 patients who had combined features of both a dopa-responsive parkinsonian syndrome and MND. RESULTS: All patients exhibited a typical clinical picture of IPS, and all were treated with levodopa or other dopaminergic drugs with good clinical response. The patients also showed clinical and electrophysiological signs of upper and/or lower motor neuron degeneration. Noticeably, in contrast to well-known distinct entities like the amyotrophic lateral sclerosis-parkinsonism/ dementia complex in southwest New Guinea, we did not observe any cognitive decline during the observation period except in 1 patient. CONCLUSION: This comorbidity of two neurodegenerative diseases supports the ongoing discussion of a pathophysiological and clinical overlap of disease processes. Due to the potent pharmacological options for the IPS symptoms in these overlap syndromes, these patients should be offered optimal symptomatic dopaminergic therapy.

Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6.

We illustrate a white caucasian patient with a severe sensorimotor neuropathy due to vitamin B6 hypervitaminosis. The patient used the pendulum to calculate his daily metabolic demands and ingested 9.6g pyridoxine/day. To our knowledge, this is the highest dosage of vitamin B6 administered to humans over prolonged periods of time ever reported in the medical literature. The unique aspect of this case is the muscle weakness and motor findings on electrophysiological testing in what is suggested by the literature to be a pure sensory neuronopathy.

Palliative care and circumstances of dying in German ALS patients using non-invasive ventilation.

Non-invasive ventilation (NIV) is known to improve quality of life and to prolong survival in amyotrophic lateral sclerosis (ALS) patients. However, little is known about the circumstances of dying in ventilated ALS patients. In the light of the debate on legalizing euthanasia it is important to provide empirical data about the process of dying in these patients. In a structured interview, 29 family caregivers of deceased ALS patients were asked about their own and the patient's attitude toward physician-assisted suicide (PAS) and euthanasia, circumstances of dying, and the use of palliative medication. Quantitative and qualitative content analysis was performed on the data. Non-recurring suicidal thoughts were reported by five patients. Three patients and seven relatives had thought about PAS. Seventeen caregivers described the patients' death as "peaceful", while choking was reported in six bulbar patients. In final stages of dying, the general practitioner (GP) was involved in the treatment of 10 patients, with palliative medication including sedatives and opiates being administered in eight cases. In conclusion, in contrast to the Netherlands, where 20% of terminal ALS patients die from PAS or euthanasia, only a small minority of our patients seems to have thought about PAS. The legal situation in Germany (where euthanasia is illegal), a bias due to the selection of NIV patients as well as a high percentage of religious patients and those with good levels of social support from family and friends, might account for this. Most of our patients died peacefully at home from carbon dioxide narcosis, but choking was described in some bulbar patients. Thus, palliative care, especially the use of opiates, anxiolytics and sedatives should be optimized, and the involvement of GP should be strongly encouraged, especially in bulbar patients.

Dropped-head syndrome due to steroid responsive focal myositis: a case report and review of the literature.

Isolated severe weakness of the paraspinal musculature, either at the cervical level leading to a "dropped head syndrome" or at the thoracic level leading to a "bent-spine syndrome", is a rare disorder. Etiologically it may be present in a variety of neurological diseases including Parkinson's disease, multiple system atrophy, neuromuscular or motor neuron diseases, as well as non-inflammatory, inflammatory, dystrophic or metabolic myopathies. We present a previously healthy 74-year-old man with a 2-month history of progressive difficulty in lifting his chin off his chest. Magnetic resonance imaging and skeletal muscle biopsy revealed an isolated myositis of the neck extensor and trapezius muscles, which responded well to steroid therapy. This case and other rare reports obtained from a systematic review of the literature indicate that in a subgroup of patients "dropped head syndrome" or "bent spine syndrome" is caused by a myositis, which emphasizes the necessity to obtain a MRI examination, as well as a muscle biopsy to diagnose this potentially treatable disease.

Cardiac involvement in patients with Becker muscular dystrophy: new diagnostic and pathophysiological insights by a CMR approach.

BACKGROUND: Becker-Kiener muscular dystrophy (BMD) represents an X-linked genetic disease associated with myocardial involvement potentially resulting in dilated cardiomyopathy (DCM). Early diagnosis of cardiac involvement may permit earlier institution of heart failure treatment and extend life span in these patients. Both echocardiography and nuclear imaging methods are capable of detecting later stages of cardiac involvement characterised by wall motion abnormalities. Cardiovascular magnetic resonance (CMR) has the potential to detect cardiac involvement by depicting early scar formation that may appear before onset of wall motion abnormalities. METHODS: In a prospective two-center-study, 15 male patients with BMD (median age 37 years; range 11 years to 56 years) underwent comprehensive neurological and cardiac evaluations including physical examination, echocardiography and CMR. A 16-segment model was applied for evaluation of regional wall motion abnormalities (rWMA). The CMR study included late gadolinium enhancement (LGE) imaging with quantification of myocardial damage. RESULTS: Abnormal echocardiographic results were found in eight of 15 (53.3%) patients with all of them demonstrating reduced left ventricular ejection fraction (LVEF) and rWMA. CMR revealed abnormal findings in 12 of 15 (80.0%) patients (p = 0.04) with 10 (66.6%) having reduced LVEF (p = 0.16) and 9 (64.3%) demonstrating rWMA (p = 0.38). Myocardial damage as assessed by LGE-imaging was detected in 11 of 15 (73.3%) patients with a median myocardial damage extent of 13.0% (range 0 to 38.0%), an age-related increase and a typical subepicardial distribution pattern in the inferolateral wall. Ten patients (66.7%) were in need of medical heart failure therapy based on CMR results. However, only 4 patients (26.7%) were already taking medication based on clinical criteria (p = 0.009). CONCLUSION: Cardiac involvement in patients with BMD is underdiagnosed by echocardiographic methods resulting in undertreatment of heart failure. The degree and severity of cardiac involvement in this population is best characterised when state-of-the-art CMR methods are applied. Further studies need to demonstrate whether earlier diagnosis and institution of heart failure therapy will extend the life span of these patients.

Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. Bulbar symptoms such as dysphagia and dysarthria are frequent features of ALS and can result in reductions in life expectancy and quality of life. These dysfunctions are assessed by clinical examination and by use of instrumented methods such as fiberendoscopic evaluation of swallowing and videofluoroscopy. Laryngospasm, another well-known complication of ALS, commonly comes to light during intubation and extubation procedures in patients undergoing surgery. Laryngeal and pharyngeal complications are treated by use of an array of measures, including body positioning, compensatory techniques, voice and breathing exercises, communication devices, dietary modifications, various safety strategies, and neuropsychological assistance. Meticulous monitoring of clinical symptoms and close cooperation within a multidisciplinary team (physicians, speech and language therapists, occupational therapists, dietitians, caregivers, the patients and their relatives) are vital.

Bilateral internal carotid artery dissections related to pregnancy and childbirth.

We illustrate a 35 years old woman presenting with acute left hemiplegia three weeks after caesarean section. Cerebral MRI demonstrated acute right frontoparietal ischemic stroke, while angiographic investigations provided acute occlusion of the proximal right internal carotid artery due to a dissection and two additional dissections of the proximal and distal contralateral internal carotid artery. A skin biopsy revealed alterations like in some types of Ehlers-Danlos syndrome. Pregnancy, caesarean section, and possibly hormonal implicated connective tissue changes may have contributed to the dissections. Remarkably a second pregnancy with a close ultrasonographic vascular monitoring two years later succeeded upon caesarean section without complications, which gives an important input in the gestational guidance of risk patients.

Granulomatous myositis mimicking slowly progressive lower motor neuron disease.

Here we illustrate a 74-year-old patient presenting with clinical signs of slowly progressive motor neuron disease. After electromyography demonstrated myopathic changes, a skeletal muscle biopsy was performed showing histological signs of granulomatous myositis. In extensive diagnostic workup underlying primary granulomas forming diseases were excluded and corticoid therapy was initiated, but without clinical effect. We want to point out that granulomatous myositis should be considered in the differential diagnosis of slowly progressive motor neuron diseases, especially in atypical clinical presentations.

Connective tissue disorders in dissections of the carotid or vertebral arteries.

Dissections of the carotid or vertebral arteries are a significant cause of ischemic stroke. Their etiology includes not only mechanical forces but also underlying arteriopathies such as Ehlers-Danlos syndrome type IV and other connective tissue disorders. Furthermore, dissections often occur spontaneously or after minor trauma in otherwise healthy individuals without clinically evident underlying aberrations. However, in some of these patients ultrastructural connective tissue changes can be detected. An overview of connective tissue disorders associated with dissections of the carotid or vertebral arteries is presented.

Classification of phenotype characteristics in adult-onset spinal muscular atrophy.

BACKGROUND/AIMS: Degenerative lower motor neuron diseases (LMND) encompass a group of rare clinically and genetically heterogeneous disorders with the hallmark of anterior horn cell degeneration in the spinal cord and brainstem. In a recently proposed classification, LMND were subdivided according to the clinical disease pattern and time course. This study was performed to investigate the clinical practicability of the classification. METHODS: In 22 patients with adult LMND (mean disease duration, 24 years), the disease course and detailed clinical, electrophysiological, magnetic resonance imaging, laboratory, and genetic investigations were analyzed. RESULTS: All patients could be assigned to the distinct disease subgroups, i.e. 11 patients to the slowly progressive generalized form (group 1), one to the distal form (group 2), 3 to the segmental distal form (group 3a), and seven to the segmental proximal form (group 3b). CONCLUSIONS: The proposed classification was confirmed to be a practicable tool, and additional implications for the classification of LMND could be drawn from the data in our patient sample.

Atypical botulism sparing palsy of extraocular muscles.

Recent studies of patients with botulism found ophthalmoplegia as a characteristic clinical sign. Here we illustrate a very rare case of atypical foodborne botulism with multiple bilateral cranial nerve palsies sparing palsy of extraocular muscles. Therefore, the classical diagnostic pentad of botulism (dry mouth, nausea, vomiting, dysphagia, diplopia, fixed dilated pupils) may be of limited sensitivity in single cases.

Benign symmetric lipomatosis with axonal neuropathy and abnormalities in specific mitochondrial tRNA regions.

Benign symmetric lipomatosis, also called Madelung's disease, is characterized by lipomata and fatty infiltrations. Involvement of the nervous system has occasionally been described, mitochondrial dysfunctions have been suggested. We report a 55 year old male suffering from benign symmetric lipomatosis with associated axonal neuropathy and hyperlipoproteinemia. He showed a remarkable phenotype of neuropathy i.e. no sensory disturbance, ubiquitous fasciculations and muscle cramps, furthermore reduced COX activity and abnormalities in specific mitochondrial tRNA regions.