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.

The influence of weaning duration on rehabilitative outcome in early neurological rehabilitation.

BACKGROUND: We investigated if longer weaning is associated with inferior rehabilitative outcome in critical illness polyneuropathy (CIP) and cerebrovascular diseases (CVD). METHODS: We analysed retrospectively weaning protocols and medical histories of 171 tracheotomized patients with CIP and CVD. We assessed weaning durations (WD), independence in activities of daily living, as assessed by the functional independence measure (FIM), mortality rates and discharge modalities in each cohort. Weaning was performed using synchronized intermittent mandatory ventilation (SIMV) with Autoflow® and assisted spontaneous ventilation (ASV). RESULTS: WD was significantly longer in CIP compared to CVD (p < 0.001). Despite shorter in-patient treatment and longer WD, patients with CIP acquired significantly greater gains of improvement than CVD (p = 0.015). Independent living at home was possible in 43% of patients with CIP and in 26% of CVD. Mortality was equal in both groups (13% vs. 6%, p > 0.05). Chronic obstructive pulmonary disease (COPD) showed a trend towards longer weaning durations in both entities (p = 0.06). Higher age significantly correlated with longer WD (p = 0.038, r = 0.16). Longer rehabilitation duration (RD) positively correlated with higher Delta-FIM (DFIM) in both entities (p = 0.006, r = 0.21). CONCLUSION: Longer weaning and its partly negative influence on rehabilitative outcome can be compensated by longer in-patient rehabilitation in CIP and CVD.

Recovery and outcome of frontal alien hand syndrome after anterior cerebral artery stroke.

Ischemic lesions within the territory of the anterior cerebral artery present with a variety of clinical signs and symptoms. Among these, frontal alien hand syndrome is rare and easily overlooked in the acute clinical setting, but significantly impacts on functional activities of daily life. Given its rareness, very little is known about its long-term outcome. To shade some more light onto this issue, clinical presentation, course of rehabilitation and outcome of two illustrative cases of frontal alien hand syndrome following anterior cerebral artery stroke are presented. Within seven and nine months from symptom onset, respectively, the clinical symptoms of frontal alien hand had resolved completely in both cases. We conclude that frontal alien hand syndrome has a favourable long-term outcome.

Mutation in the mitochondrial tRNA(Ile) gene causes progressive myoclonus epilepsy.

PURPOSE: The group of the rare progressive myoclonic epilepsies (PME) include a wide spectrum of mitochondrial and metabolic diseases. In juvenile and adult ages, MERRF (myoclonic epilepsy with ragged red fibres) is the most common form. The underlying genetic defect in most patients with the syndrome of MERRF is a mutation in the tRNALys gene, but mutations were also detected in the tRNAPhe gene. METHOD: Here, we describe a 40 year old patient with prominent myoclonic seizures since 39 years of age without a mutation in the known genes who underwent intensive clinical, genetic and functional workup. RESULTS: The patient had a slight mental retardation and a severe progressive hearing loss based on a defect of the inner ear on both sides. Ictal electroencephalography (EEG) showed bilateral occipital and generalized spikes and polyspikes induced and aggravated by photostimulation. A cranial magnetic resonance imaging (cMRI) detected a global cortical atrophy of the brain and mild periventricular white matter lesions. The electromyography (EMG) was normal but the muscle biopsy showed abundant ragged red fibres. Sequencing of the mitochondrial DNA from the skeletal muscle biopsy revealed a novel heteroplasmic mutation (m.4279A>G) in the tRNAIle gene which was functionally relevant as tested in single skeletal muscle fibre investigations. CONCLUSION: Mutations in tRNAIle were described in patients with chronic progressive external ophthalmoplegia (CPEO), prominent deafness or cardiomyopathy but, up to now, not in patients with myoclonic epilepsy. The degree of heteroplasmy of this novel mitochondrial DNA mutation was 70% in skeletal muscle but only 15% in blood, pointing to the diagnostic importance of a skeletal muscle biopsy also in patients with myoclonic epilepsy.

Parkinsonism following bilateral hypoxic-ischemic lesions of the striatum.

A 40-year-old white male received cardio-pulmonary resuscitation after cardiac arrest due to an epileptic status. Four months after the incident he developed an akinetic-rigid syndrome and a postural tremor more pronounced on the right side of the body. Brain imaging revealed bilateral lesions of the putamen and caudate nucleus. Levodopa improved bradykinesia and muscular rigidity, but not the postural tremor.

Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy.

BACKGROUND: Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies. METHODS AND RESULTS: In a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted "edema" imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments. CONCLUSIONS: Cardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in patients suffering from the subforms CPEO or KSS.

CMR gives clue to "ragged red fibers" in the heart in a patient with mitochondrial myopathy.

Mitochondrial myopathy may manifest either as isolated myopathy or as a neuromuscular multisystemic disease and is caused by genetic defects in the mitochondrial genome resulting in respiratory chain disorders. MELAS, which is characterised by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes due to gene mutations in the mitochondrial DNA (adenine-to-guanine transition at nucleotide pair 3243, m.3243A>G), constitutes such a mitochondrial multisystemic disease. Although hypertrophied or dilated cardiomyopathy is quite common in MELAS, there have been no cardiovascular magnetic resonance (CMR)-based studies in these patients so far. This case report represents the first case in which comprehensive CMR and endomyocardial biopsy (EMB) data were obtained in the same patient with mitochondrial myopathy. Late gadolinium enhancement (LGE) imaging demonstrated a unique pattern of myocardial damage and histological work-up revealed the presence of "ragged red fibers" (conglomerates of mitochondria) in the heart tissue verifying the diagnosis of a mitochondrial cardiomyopathy as part of the underlying mitochondrial disease MELAS.

Cardiovascular magnetic resonance reveals similar damage to the heart of patients with Becker and limb-girdle muscular dystrophy but no cardiac symptoms.

Cardiac involvement in patients with a sarcoglycanopathy (limb-girdle muscular dystrophy) has been described previously; however, this is the first cardiovascular magnetic resonance (CMR) study in such a patient demonstrating an interesting pattern of myocardial damage using late gadolinium enhancement (LGE) imaging. Moreover, the wall motion abnormality and the subepicardial pattern of LGE in this patient with a sarcoglycanopathy is in agreement with the findings in another patient with Becker muscular dystrophy. The predominance of LGE in the subepicardial layers of the left ventricular inferolateral wall suggests that such a myocardial damage pattern represents a nonspecific cardiac phenotype in response to exaggerated mechanical stress in this region, at least in patients with a sarcoglycanopathy or dystrophinopathy.

Histopathological analysis of skeletal muscle in patients with Parkinson's disease and 'dropped head'/'bent spine' syndrome.

BACKGROUND: 'Dropped head' and 'bent spine' phenomena are recognized clinical presentations of neuromuscular disorders. Similar symptoms are known in patients with parkinsonian syndromes, but their pathophysiology remains unclear. One hypothesis is a relation between the movement disorder and the skeletal muscle pathology. METHODS: We describe detailed histopathological data from 19 consecutive skeletal muscle biopsies in patients with idiopathic Parkinson's disease (PD) and concomitant 'dropped head' or 'bent spine' syndrome. A biochemical analysis of the respiratory chain complexes was also performed, and clinical, electrophysiological, and imaging data were analyzed. RESULTS: The subjects developed neuromuscular symptoms 2.7 +/- 2.4 years after onset of PD. We found no correlation with the age at onset of the disease, disease duration, or severity. We found no evidence for dystonia nor did we find any relationship between their anti-parkinsonian medication, and possible drug side effects. Muscle biopsies were abnormal in all patients. Based on histopathological criteria we divided the muscle pathology into three different groups, i.e. necrotizing myopathy, inflammatory myopathy, and myopathy with mitochondrial abnormalities. Biochemical analysis of respiratory chain complexes revealed abnormalities in nine patients. CONCLUSIONS: 'Dropped head' and 'bent spine' symptoms in association with PD appear to be accompanied by a wide spectrum of histopathological abnormalities in skeletal muscle. A muscle biopsy should be performed to identify potentially treatable conditions (i.e. inflammatory myopathies).

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.

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.