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Background: Acute basilar artery occlusion is a life-threatening medical emergency with a highly elevated mortality rate when left untreated. Little is known about symptoms and clinical progression of chronic occlusions. The aim of this study was to systematically analyze the clinical presentation of patients with chronic basilar artery occlusion (CBAO). Methods: Monocentric retrospective analysis of adult patients with CBAO was treated between 2015 and 2023 in the Department of Neurology, Klinikum Kassel. Inclusion criteria were basilar artery occlusion without brainstem infarction as well as patients with a basilar artery occlusion in whom revascularization could not be achieved and a follow-up period of at least 3 months. Results: A total of 15 patients were found. In five patients basilar artery occlusion was diagnosed as an incidental finding, four patients had neurological symptoms but no proven brainstem infarction (3 × transient ischemic attack, 1 × isolated posterior artery infarct) and six patients presented with acute basilar artery occlusion and a follow-up > 3 months. The most common site of occlusion was midbasilar (80%, n = 12), isolated (n = 7) or in combination with other locations (n = 5). In all cases collateralization could be demonstrated by the posterior communicating arteries. The most common vascular risk factors (VRF) were hypertension (100%) and hypercholesterolemia (67%). Conclusions: Patients with CBAO may present with only mild symptoms or may even be asymptomatic. This condition may be survived for a long time. The high percentage of vascular risk factors and further cerebral vessel occlusions suggest arteriosclerosis as the major causing factor of CBAO. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder with a wide clinical variability. Contractions of the D4Z4 macrosatellite repeat on chromosome 4q35 are the molecular basis of the pathophysiology. Recently, in a subset of patients without D4Z4 repeat contractions, variants in the SMCHD1 gene have been identified that lead to hypomethylation of D4Z4 and thus DUX4 transcription, which causes FSHD type 2. In this study, we have screened 55 FSHD1-negative and 40 FSHD1-positive patients from unrelated families for potentially pathogenic variants in SMCHD1 by next-generation sequencing (NGS). We identified variants in SMCHD1 in 11 index patients, including missense, splice site and non-sense mutations. We developed a pyrosequencing assay to determine the methylation status of the D4Z4 repeat array and found significantly lower methylation levels for FSHD2 patients than for healthy controls and FSHD1 patients. Two out of eleven SMCHD1 mutation carriers had moderately contracted D4Z4 alleles thus these patients are suffering from FSHD1 and 2. Comparing the phenotype of patients, all FSHD2 patients were relatively mildly affected while patients with FSHD1+2 were much more severely affected than expected from their D4Z4 copy number. Our findings confirm the role of SMCHD1 mutations in FSHD2 and as a modifier of disease severity. With SMCHD1 variants found in 16.4% of phenotypic FSHD patients without D4Z4 repeat contractions, the incidence of FSHD2 is rather high and hence we suggest including sequencing of SMCHD1, haplotyping and methylation analysis in the workflow of molecular FSHD diagnostics. [ABSTRACT FROM AUTHOR]

Purpose: The objective of our trial was to obtain more comprehensive data on the risks and benefits of kinetic therapy in intensive care patients with intracerebral pathology. Methods: Standardized data of prone positioning in our NeuroIntensive Care Unit were collected from 2007 onward. A post hoc analysis of all available data was undertaken, with special consideration given to values of intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygenation in correlation to prone (PP), or supine positioning (SP) of patients. Cases were considered eligible if kinetic therapy and ICP were documented. Prone positioning was performed in a 135° position for 8 h per treatment unit. Results: A total of 115 patients treated with prone positioning from 2007 to 2013 were identified in our medical records. Of these, 29 patients received ICP monitoring. Overall, 119 treatment units of prone positioning with a mean duration of 2.5 days per patient were performed. The mean baseline ICP in SP was 9.5 ± 5.9 mmHg and was increased significantly during PP ( p < 0.0001). There was no significant difference between CPP in SP (82 ± 14.5 mmHg) compared to PP ( p > 0.05). ICP values >20 mmHg occurred more often during PP than SP ( p < 0.0001) and were associated with significantly more episodes of decreased CPP <70 mmHg ( p < 0.0022). The mean paO/FiO ratio (P/F ratio) was increased significantly in prone positioning of patients ( p < 0.0001). Conclusions: The analyzed data allow a more precise understanding of changes in ICP and oxygenation during prone positioning in patients with acute brain injury and almost normal baseline ICP. Our study shows a moderate, yet significant elevation of ICP during prone positioning. However, the achieved increase of oxygenation by far exceeded the changes in ICP. It is evident that continuous monitoring of cerebral pressure is required in this patient group. [ABSTRACT FROM AUTHOR]

Familial amyloid polyneuropathy (FAP) is a progressive systemic autosomal dominant disease caused by pathogenic mutations in the transthyretin ( TTR) gene. We studied clinical, electrophysiological, histopathological, and genetic characteristics in 15 (13 late-onset and two early-onset) patients belonging to 14 families with polyneuropathy and mutations in TTR. In comparison, we analysed the features of nine unrelated patients with an idiopathic polyneuropathy, in whom TTR mutations have been excluded. Disease occurrence was familial in 36 % of the patients with TTR-associated polyneuropathy and the late-onset type was observed in 86 % (mean age at onset 65.5 years). Clinically, all late-onset TTR-mutant patients presented with distal weakness, pansensory loss, absence of deep tendon reflexes, and sensorimotor hand involvement. Afferent-ataxic gait was present in 92 % leading to wheelchair dependence in 60 % after a mean duration of 4.6 years. Autonomic involvement was observed in 60 %, and ankle edema in 92 %. The sensorimotor polyneuropathy was from an axonal type in 82 %, demyelinating or mixed type in 9 % each. Compared to the TTR-unmutated idiopathic polyneuropathy patients, we identified rapid progression, early ambulatory loss, and autonomic disturbances, associated with a severe polyneuropathy as red flags for TTR–FAP. In 18 % of the late-onset TTR-FAP patients, no amyloid was found in nerve biopsies. Further diagnostic pitfalls were unspecific electrophysiology, and coincident diabetes mellitus (23 %) or monoclonal gammopathy (7 %). We conclude that a rapid disease course, severely ataxic gait, hand involvement, and autonomic dysfunction are diagnostic hallmarks of late-onset TTR–FAP. Genetic analysis should be performed even when amyloid deposits are lacking or when polyneuropathy-causing comorbidities are concomitant. [ABSTRACT FROM AUTHOR]

Background: Physiotherapy plays an important role in the therapy of patients with acute cerebral diseases. Studies concerning the effects of physiotherapy on intracerebral pressure (ICP) and cerebral perfusion pressure (CPP) are, however, rare. Methods: An observational study was performed on critically ill patients who were receiving ICP measurements and who were treated with passive range of motion (PROM) on our neuro-intensive care unit. ICP, CPP, mean arterial pressure (MAP) and heart rate were recorded continuously every minute, beginning 15 min before, during (26 min) and 15 min after treatment with PROM. Patients with mean ICP <15 mmHg (Group 1) and patients with mean ICP ≥15 mmHg (Group 2) before physiotherapy were analyzed separately. Results: Overall there were 84 patients (f:m = 1:1) with 298 treatments units, 224 in Group 1 and 74 in Group 2, respectively. Mean ICP before treatment was 11.5 ± 5.1 mmHg, with a significant decrease of 1 mmHg during therapy ( p = 2.0e-10). This was also true for Group 1 (baseline ICP 9.4 ± 3.7 mmHg, decrease of 0.7 mmHg, p = 3.8e-6) and Group 2 (baseline ICP 18.1 ± 2.7 mmHg, decrease of 2 mmHg, p = 3.7e-6). However, a persistent ICP reduction after therapy was seen only in Group 2. There were no significant differences between mean CPP and MAP comparing ICP before and after PROM in all groups. No adverse side effects of PROM were observed. Conclusions: Physiotherapy with PROM can be used safely in patients with acute neurological diseases, even if ICP is elevated before therapy. [ABSTRACT FROM AUTHOR]

Background: Bedside percutaneous tracheostomy (PT) is very commonly used for patients who require prolonged mechanical ventilation. The effect of tracheostomy on intracranial pressure (ICP) is currently a subject of controversy. The aim of our study is to clarify the relation between PT and its effect on ICP and cerebral perfusion pressure. Methods: 38 patients on our intensive care unit were included prospectively in an observational study. We examined mean values of HF, SpO, ICP, CPP, and MAP for changes over five different phases of the procedure using paired Mann-Whitney U tests. A p value of <0.05 was considered significant. p values were Bonferroni corrected for multiple testing. Results: PT was performed on 38 patients ( f = 19, m = 19; mean = 56 years). Median ICP before intervention was 9 mmHg. During positioning of the patient, ICP had risen to 14, during bronchoscopy to 16, and during tracheostomy to 18 mmHg, all being significantly higher than baseline level. Monitoring of MAP showed a significant increase to 101 mmHg only during tracheostomy. SpO and HF did not show any significant changes. Mean duration of positioning, bronchoscopy and tracheostomy was 19, 10, and 17 min. 8 patients received osmotherapy due to a rise of ICP of more than 30 mmHg. Conclusion: PT only leads to a significant rise of ICP during the procedure. Nevertheless, therapy of ICP is necessary in some patients. From our point of view, therefore, tracheostomy should only be performed under continuous monitoring of ICP and CPP in patients with severe cerebral dysfunctions and critically elevated ICP. [ABSTRACT FROM AUTHOR]

Mutations in THAP1 have been associated with dystonia 6 (DYT6). THAP1 encodes a transcription factor that represses the expression of DYT1. To further evaluate the mutational spectrum of THAP1 and its associated phenotype, we sequenced THAP1 in 567 patients with focal (n=461), segmental (n=68), or generalized dystonia (n=38). We identified 10 novel variants, including six missense substitutions within the DNA-binding Thanatos-associated protein domain (Arg13His, Lys16Glu, His23Pro, Lys24Glu, Pro26Leu, Ile80Val), a 1bp-deletion downstream of the nuclear localization signal (Asp191Thrfs*9), and three alterations in the untranslated regions. The effect of the missense variants was assessed using prediction tools and luciferase reporter gene assays. This indicated the Ile80Val substitution as a benign variant. The subcellular localization of Asp191Thrfs*9 suggests a disturbed nuclear import for this mutation. Thus, we consider six of the 10 novel variants as pathogenic mutations accounting for a mutation frequency of 1.1%. Mutation carriers presented mainly with early onset dystonia (<12 years in five of six patients). Symptoms started in an arm or neck and spread to become generalized in three patients or segmental in two patients. Speech was affected in four mutation carriers. In conclusion, THAP1 mutations are rare in unselected dystonia patients and functional analysis is necessary to distinguish between benign variants and pathogenic mutations. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit unspecific morphological signs of a degenerative myopathy. We report on five unrelated patients who carried the pathogenic FSHD mutation on chromosome 4q35. Muscle biopsies revealed numerous rimmed vacuoles and filamentous cytoplasmic inclusions in all cases. Clinically, the patients suffered from weakness and atrophy predominantly of the lower limb muscles. In conclusion, we suggest considering FSHD in the differential diagnosis of adult-onset distal myopathies with rimmed vacuoles. [ABSTRACT FROM AUTHOR]

Age is the most important risk factor for developing a stroke. In addition, age may also influence stroke recovery. To allow structured discharge planning, it may be important to consider the influence of age on stroke recovery during the early phase. We studied the effect of patient age on early stroke recovery in a cohort of 2219 unselected stroke patients. Data on functional status (Barthel Index Score) were collected prospectively within 24h after admission, after one week and at discharge for 2219 acute stroke patients treated in 1999 and 2000 at 7 neurological departments in the county of Hesse, Germany. Multiple regression analyses were used to test for an association between age, relative recovery and speed of recovery of ADL after stroke. More than half of the patients (58 %) improved in functional status during hospitalization. 37 % had no change in Barthel Index score and only a small number of patients (5 %) deteriorated during this period. Relative improvement decreased with increasing age: patients younger than 55 years showed an improvement of 67 % of the maximum possible improvement compared whith only 50 % for patients above 55 years (adjusted R2 = 0.120, βage = -0.130, p < 0.001). Age only had a small effect on the speed of recovery. For younger patients functional recovery was slightly faster (adjusted R2 = 0.256, βage = -0.080, p < 0.001). Despite its strong influence on case fatality, age is a poor predictor of functional recovery during the very early phase after stroke. Resulting functional recovery depends much more on the extent of the initial disability. Advanced age should not be regarded as a limiting factor in the early rehabilitation of stroke patients. [ABSTRACT FROM AUTHOR]

We studied the diagnostic value of computed tomographic angiography (CTA) in the posterior circulation as a noninvasive substitute for intra-arterial digital subtraction angiography (DSA). We prospectively investigated 103 patients with acute stroke in the posterior circulation. All patients underwent CTA and Doppler ultrasound, and DSA was performed in 22 patients. Vascular findings were classified in categories according to the type of lesion and the location in the vertebral, basilar, or posterior cerebral artery. In the first part of the analysis we examined the correlation between CTA and intra-arterial DSA (n=22), and in the second part that between CTA and Doppler ultrasound (n=103). Intra-arterial DSA identified 11 stenoses, 13 occlusions, and 3 hypoplasias. The correlation between DSA and CTA was best before the basilar artery (all lesions were identified with CTA). Of the 14 lesions detected in the vertebral artery by DSA 13 were also detected by CTA, but the specific type of lesion was identified in only 7 cases. The correlation between CTA and Doppler ultrasound was lower. In conclusion, CTA is thus a reliable method for detecting lesions in the posterior circulation and may replace DSA in many cases. However, particularly in the vertebral artery DSA remains in the superior technique. [ABSTRACT FROM AUTHOR]

Clinical and electrophysiological findings are described in three patients with hereditary motor and sensory neuropathy in association with optic atrophy (HMSN VI). The optic atrophy was of the Leber type in a 15-year-old boy. In a 70-year-old patient, as in three members of his family, optic atrophy was associated with tapetoretinal degeneration. In addition to HMSN and optic atrophy a 20-year-old man suffered from sensorineural deafness. Electrophysiological studies indicated a neuronal form of neuropathy, as in HMSN II. Brainstem auditory evoked potentials also revealed subclinical involvement of the central auditory pathways in the patients without hearing defects. [ABSTRACT FROM AUTHOR]

An open prospective multicentric therapeutic trial to determine the timing and type of therapeutic intervention in patients presenting with secondary deterioration following cerebellar stroke is described. According to the results of retrospective studies a controlled approach comparing different therapies is ethically not feasible. Participants use the same scores and protocol for patient data collection but many choose different therapeutic procedures. [ABSTRACT FROM AUTHOR]