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Advances in the Diagnosis and Treatment of Brain Damage

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Brain Injury".

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 9925

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Special Issue Editor

Dr. Markus C. Kowarik

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Guest Editor

Department of Neurology & Stroke, and Hertie-Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, D-72076 Tübingen, Germany
Interests: neuroimmunology; multiple sclerosis; neuromyelitis optica spectrum disease; B cells; oncoimmunology

Special Issue Information

Dear Colleagues,

There are multiple pathophysiological conditions, including neurovascular diseases, neuro-trauma, infectious diseases, neurodegenerative diseases, tumors, and neuroinflammation, which lead to brain damage and are associated with various clinical symptoms. Although huge advances with regards to molecular diagnostics and MRI have been made during clinical work-up, differential diagnoses might still be challenging, it is often difficult to predict future disease courses, and the clinical presentation is not always reflected by corresponding brain lesions on MRI. Despite growing treatment options that address direct pathophysiological mechanisms, the brain is a highly complex organ that is still challenging to treat and multiple diseases can only be treated symptomatically.

With this Special Issue, we hope to encourage submissions that discuss the current state-of-the-art of both clinical and radiological features of brain damage, molecular aspects (such as serum or CSF markers in different diseases), newly evolving diagnostic tools, and therapies (such as neuro-regenerative treatments), as well as address challenges and ongoing controversies.

Dr. Markus C. Kowarik
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

brain damage
clinical presentation
MRI
clinical radiological correlation
CNS biomarkers
CNS-specific treatments
neurodegenerative treatments

Published Papers (9 papers)

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Research

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14 pages, 1838 KiB

Open AccessArticle

Feasibility of Fluid Responsiveness Assessment in Patients at Risk for Increased Intracranial Pressure

by Aleksandar R. Zivkovic, Aleko Kjaev, Silvia Schönenberger, Sandro M. Krieg, Markus A. Weigand and Jan-Oliver Neumann

J. Clin. Med. 2024, 13(6), 1786; https://doi.org/10.3390/jcm13061786 - 20 Mar 2024

Viewed by 559

Abstract

Background: Effective fluid management is important for patients at risk of increased intracranial pressure (ICP). Maintaining constant cerebral perfusion represents a challenge, as both hypovolemia and fluid overload can severely impact patient outcomes. Fluid responsiveness tests, commonly used in critical care settings, are often deemed potentially hazardous for these patients due to the risk of disrupting cerebral perfusion. Methods: This single-center, prospective, clinical observational study enrolled 40 patients at risk for increased ICP, including those with acute brain injury. Informed consent was obtained from each participant or their legal guardians before inclusion. The study focused on the dynamics of ICP and cerebral perfusion pressure (CPP) changes during the Passive Leg Raise Test (PLRT) and the End-Expiratory Occlusion Test (EEOT). Results: The results demonstrated that PLRT and EEOT caused minor and transient increases in ICP, while consistently maintaining stable CPP. EEOT induced significantly lower ICP elevations, making it particularly suitable for use in high-risk situations. Conclusions: PLRT and EEOT can be considered feasible and safe for assessing fluid responsiveness in patients at risk for increased ICP. Notably, EEOT stands out as a preferred method for high-risk patients, offering a dependable strategy for fluid management without compromising cerebral hemodynamics. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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11 pages, 1093 KiB

Open AccessArticle

The Effects of Neuromonitoring and Cerebrolysin Administration on Outcomes in Patients with Traumatic Brain Injury—An Interventional Pilot Study

by Konrad Jarosz, Klaudyna Kojder, Karolina Skonieczna-Żydecka, Agata Andrzejewska, Joanna Sołek-Pastuszka and Anna Jurczak

J. Clin. Med. 2024, 13(2), 353; https://doi.org/10.3390/jcm13020353 - 8 Jan 2024

Viewed by 907

Abstract

Introduction: Traumatic brain injury (TBI) is one of the most common causes of death and an important burden to the worldwide healthcare system and society. There is a lack of guidelines for types of monitoring or neuroprotective therapy. The aim of this pilot study was to assess its feasibility and, furthermore, to evaluate the impact of Cerebrolysin on the following clinical outcomes: length of stay, Glasgow Outcome Scale (GOS) and mortality. Methods: A cohort of 56 patients was included in this non-randomised, real-time, pre–post-interventional study. The patients were assessed with the Glasgow Coma Scale (GCS) and divided into two groups: severe (GCS < 8) and non-severe (GCS > 8). After the radiological examination (CT scan), the patients were qualified for an immediate neurosurgical procedure if needed. The patients were admitted to the intensive care unit, where a standardised protocol for TBI treatment was implemented. Additional neuromonitoring was applied. Results: There were 56 patients (19 females; 33.9%), of which 41 were considered severe cases; the patients were allocated to the Cerebrolysin (n = 25) or control groups (n = 31). In a generalised linear model (GLM) approach, the use of Cerebrolysin was associated with a decrease in the probability of death in non-severe patients (by 0.333 (standard error (SE) = 0.157, p = 0.034)) but not in severe patients (estimate (Est.) = −0.115, SE = 0.127, p = 0.364). Patients who received Cerebrolysin and who were neuromonitored had favourable outcomes and better survival rates. Conclusions: A multimodal treatment approach with monitoring and Cerebrolysin may have a beneficial effect on patients with less severe TBIs; however, the present study has multiple limitations, and further research is needed. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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11 pages, 294 KiB

Open AccessArticle

Free Thyroxine (fT4) as a Potential Biomarker of Neurological and Functional Outcome in Acquired Brain Injury: A Prospective Multicenter Cohort Study

by Chiara Mele, Sergio Bagnato, Antonio De Tanti, Lucia Francesca Lucca, Donatella Saviola, Laura Marcuccio, Pasquale Moretta, Federico Scarponi, Ernesto Losavio, Emilia Picciola and Valeria Pingue

J. Clin. Med. 2023, 12(23), 7433; https://doi.org/10.3390/jcm12237433 - 30 Nov 2023

Viewed by 581

Abstract

The potential involvement of thyroid hormones (THs) in the neurological and functional recovery of patients with brain damage has been hypothesized. We aimed at investigating the role of THs and their variations during the rehabilitation process as predictive biomarkers of neurological and functional outcome in patients with acquired brain injury (ABI). This prospective, multicenter cohort study included 220 patients with ABI consecutively admitted for a 6-month neurorehabilitation program. Data on the etiology of the brain injury, occurrence of seizures, neurosurgical procedures, and death during hospitalization were collected. Both at the baseline (T0) and at the end of the rehabilitation process (T1), the following variables were evaluated: thyroid function (TSH, fT4, and fT3) and outcome measure including the Glasgow Coma Scale (GCS), Glasgow Outcome Scale-Extended (GOS-E), and Functional Independence Measure (FIM) scale. During neurorehabilitation, a significant decrease in fT4 levels was documented in the population as a whole and in patients with severe ABI (p < 0.0001), whereas no significant variations were found in TSH and fT3 levels. No significant associations were found between THs and seizure occurrence, while the neurological and functional outcomes were associated with the variation in fT4 levels during rehabilitation. In particular, a higher magnitude of decrease in fT4 levels emerged as an independent predictor of more severe neurological damage (OR = 3.48, CI 95% 1.04–11.69, p = 0.04) and a lower functional recovery (β = −0.22, p = 0.01). In conclusion, serum fT4 variation during neurorehabilitation could represent a potential biomarker of neurological and functional outcome in patients with ABI. Further studies are needed to investigate the mechanisms underlying this association. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

13 pages, 2338 KiB

Open AccessArticle

Gender and Age Differences in Outcomes after Mild Traumatic Brain Injury

by Sophia Wågberg, Britt-Marie Stålnacke and Beatrice M. Magnusson

J. Clin. Med. 2023, 12(15), 4883; https://doi.org/10.3390/jcm12154883 - 25 Jul 2023

Cited by 2 | Viewed by 794

Abstract

Many people who suffer traumatic brain injury (TBI) have long-term residual symptoms. This study evaluates post-TBI symptoms and disabilities seven to eight years after mild TBI (mTBI), with specific aims to evaluate gender and age differences, and whether repeated TBI leads to the deterioration of symptoms and function. Telephone interviews with 595 patients were conducted using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) to assess post-TBI symptoms, and the Glasgow Outcome Scale Extended (GOSE) was used to assess disability. Thirty-four percent reported post-concussion symptoms (40% of females and 29% of males). The symptom burden was higher in women than in men, and higher in patients with repeated TBI. The distribution of symptoms was similar for women and men. Women reported a significantly higher level of disability on GOSE; 31% had not returned fully to daily life, compared with 17% of men (p < 0.001), the biggest difference being in the age group of 25–49 years. Patients with repeated mTBI reported significantly lower scores on GOSE; 31% had not returned fully to daily life, compared with 21% of the single-TBI patients (p < 0.05). After mild TBI, one of three patients reported at least one post-TBI symptom. Women and individuals with repeated TBI presented a worse GOSE outcome. These findings have implications for clinical practice and research and should be taken into consideration when planning the rehabilitation and follow-up of mTBI patients. This also emphasises the importance of informing patients about post-concussion symptoms and when to seek healthcare. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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13 pages, 609 KiB

Open AccessArticle

Optical Coherence Tomography: Retinal Imaging Contributes to the Understanding of Brain Pathology in Classical Galactosemia

by Amelie S. Lotz-Havla, Tara Christmann, Klaus G. Parhofer, Esther M. Maier and Joachim Havla

J. Clin. Med. 2023, 12(5), 2030; https://doi.org/10.3390/jcm12052030 - 3 Mar 2023

Cited by 1 | Viewed by 1285

Abstract

It remains unresolved whether central nervous system involvement in treated classical galactosemia (CG) is a progressive neurodegenerative process. This study aimed to investigate retinal neuroaxonal degeneration in CG as a surrogate of brain pathology. Global peripapillary retinal nerve fibre layer (GpRNFL) and combined ganglion cell and inner plexiform layer (GCIPL) were analysed in 11 CG patients and 60 controls (HC) using spectral–domain optical coherence tomography. Visual acuity (VA) and low-contrast VA (LCVA) were acquired to test visual function. GpRNFL and GCIPL did not differ between CG and HC (p > 0.05). However, in CG, there was an effect of intellectual outcome on GCIPL (p = 0.036), and GpRNFL and GCIPL correlated with neurological rating scale scores (p < 0.05). A single-case follow-up analysis showed GpRNFL (0.53–0.83%) and GCIPL (0.52–0.85%) annual decrease beyond the normal aging effect. VA and LCVA were reduced in CG with intellectual disability (p = 0.009/0.006), likely due to impaired visual perception. These findings support that CG is not a neurodegenerative disease, but that brain damage is more likely to occur early in brain development. To clarify a minor neurodegenerative component in the brain pathology of CG, we propose multicenter cross-sectional and longitudinal studies using retinal imaging. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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12 pages, 8835 KiB

Open AccessArticle

Clinical-Radiological Mismatch in Multiple Sclerosis Patients during Acute Relapse: Discrepancy between Clinical Symptoms and Active, Topographically Fitting MRI Lesions

by Jutta Dünschede, Christoph Ruschil, Benjamin Bender, Annerose Mengel, Tobias Lindig, Ulf Ziemann and Markus C. Kowarik

J. Clin. Med. 2023, 12(3), 739; https://doi.org/10.3390/jcm12030739 - 17 Jan 2023

Viewed by 1439

Abstract

Background: Relapses in multiple sclerosis (MS) patients are usually defined as subacute clinical symptoms that last for at least 24 h. To validate a clinical relapse on magnetic resonance imaging (MRI), an anatomically fitting lesion with gadolinium enhancement in the central nervous system (CNS) would be mandatory. The aim of this study was to validate clinical relapses in regard to the concomitant detection of active, anatomically fitting MRI lesions. Methods: We performed a retrospective analysis of 199 MS patients with acute relapse who had received an MRI scan before the initiation of methylprednisolone (MPS) therapy. Clinical data and MRIs were systematically reanalyzed by correlating clinical symptoms with their anatomical representation in the CNS. Patients were then categorized into subgroups with a clinical-radiological match (group 1) or clinical-radiological mismatch (group 2) between symptoms and active, topographically fitting lesions and further analyzed in regard to clinical characteristics. Results: In 43% of our patients, we observed a clinical-radiological mismatch (group 2). Further analysis of patient characteristics showed that these patients were significantly older at the time of relapse. MS patients in group 2 also showed a significantly longer disease duration and significantly more previous relapses when compared to group 1. Comparing symptom clusters, the appearance of motor dysfunction during the current relapse was significantly more frequent in group 2 than in group 1. The overall dose of MPS treatment was significantly lower in group 2 than in group 1 with a similar treatment response in both groups. Conclusions: The substantial clinical-radiological mismatch during acute relapse in our study could be explained by several factors, including a psychosomatic component or disturbance of network connectivity. Alternatively, secondary progression or a diffuse neuro-inflammatory process might cause clinical symptoms, especially in older patients with a longer disease duration. As a consequence, treatment of clinical relapses and the definition of breakthrough disease should be reconsidered in regard to combined clinical and MRI criteria and/or additional biomarkers. Further studies are necessary to address the contribution of diffuse neuro-inflammation to the clinical presentation of symptoms. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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11 pages, 717 KiB

Open AccessArticle

Mechanical Thrombectomy in Cerebral Venous Sinus Thrombosis: Reports of a Retrospective Single-Center Study

by Farzaneh Jedi, Gero Dethlefs, Till-Karsten Hauser, Florian Hennersdorf, Annerose Mengel, Ulrike Ernemann and Benjamin Bender

J. Clin. Med. 2022, 11(21), 6381; https://doi.org/10.3390/jcm11216381 - 28 Oct 2022

Cited by 4 | Viewed by 1921

Abstract

Current standard care for acute cerebral venous sinus thrombosis (CVST) includes either intravenous heparin or subcutaneous low-molecular-weight heparin, but patients with refractory CVST, despite adequate anticoagulation therapy, may benefit from mechanical thrombectomy (MT). A retrospective study of patients with CVST, who underwent MT between 2011 and 2019, was performed looking at procedure success rate and clinical outcomes. Two raters evaluated the cerebral venous system of every patient before and after the intervention using the following scoring system: (0) No obvious thrombosis; (1) thrombosis without impaired blood flow; (2) thrombosis with impaired blood flow; (3) and thrombosis with complete vascular occlusion. The success of MT was measured using a score quotient (Q = A/B), dividing the sum of the patient’s scores after the intervention (A) by the sum of scores before the intervention (B). Overall, 21 MTs were performed on 20 patients with refractory or severe CVST. Clinical improvement was seen in 61.9% during hospital stay and in 80% at 6-month follow-up, with complete recovery in 70% of patients. Patients with favorable outcomes had significantly lower recanalization quotients (p = 0.008). Our study provides evidence supporting that MT may be a safe and effective treatment with favorable clinical outcomes for selected patients with CVST. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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Other

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6 pages, 1102 KiB

Open AccessCase Report

Diagnosis of Froin’s Syndrome by Parallel Analysis of Ventriculoperitoneal Shunt and Lumbar Cerebrospinal Fluid in a Patient with Cervical Spinal Stenosis

by Franca Laura Fries, Benedict Kleiser, Patricia Schwarz, Maria P. Tieck, Kornelia Laichinger, Annerose Mengel, Ulf Ziemann and Markus C. Kowarik

J. Clin. Med. 2023, 12(15), 5012; https://doi.org/10.3390/jcm12155012 - 30 Jul 2023

Viewed by 1013

Abstract

Elevated protein levels in cerebrospinal fluid (CSF) can occur in various pathologies and are sometimes difficult to interpret. We report a 62-year-old male patient with subacute neurological deterioration, progressive tetraparesis, and cytoalbumin dissociation in the lumbar CSF. The patient had a pre-existing cervical spinal stenosis with mild tetraparesis. Based on the initial cytoalbumin dissociation (protein 938 mg/dL, 4 leucocytes/µL), Guillain–Barré syndrome was initially considered. For further diagnosis, a CSF sample was taken from a pre-existing ventriculoperitoneal shunt, which showed a normal protein and cell count considering the patient’s age (protein 70 mg/dL, 1 leucocyte/µL). In conclusion, we suggest that intermediate aggravation of tetraparesis was due to pneumonia with septic constellation, and the cytoalbumin dissociation was interpreted as Froin’s syndrome (FS) due to spinal stenosis. In this unique case, we were able to prove the -often suspected- case of FS by parallel analysis of ventriculoperitoneal shunt and lumbar CSF. The triad of xanthochromia, high protein levels, and marked coagulation was first described by Georges Froin and occurs in various processes leading to severe spinal stenosis. The altered composition of lumbar CSF might be due to impaired CSF circulation; however, the exact mechanisms of this phenomenon require further investigation. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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11 pages, 1389 KiB

Open AccessCase Report

Right Transcephalic Ventriculo-Subclavian Shunt in the Surgical Treatment of Hydrocephalus—An Original Procedure for Drainage of Cerebrospinal Fluid into the Venous System

by Mircea Liţescu, Daniel Alin Cristian, Violeta Elena Coman, Anwar Erchid, Iancu Emil Pleşea, Anca Bordianu, Corina Veronica Lupaşcu-Ursulescu, Costin George Florea, Ionuţ Simion Coman and Valentin Titus Grigorean

J. Clin. Med. 2023, 12(15), 4919; https://doi.org/10.3390/jcm12154919 - 26 Jul 2023

Viewed by 857

Abstract

The objectives of this article are to present an original surgical procedure for the temporary or definitive resolution of hydrocephalus, in the case of repeated failure of standard treatment techniques, and to present a case that was resolved using this surgical technique. Materials and methods: We present the case of a 20-year-old male patient with congenital hydrocephalus who underwent a number of 39 shunt revisions, given the repetitive dysfunctions of various techniques (ventriculo-peritoneal shunt, ventriculo-cardiac shunt). The patient was evaluated with the ventricular catheter externalized at the distal end and it was necessary to find an emergency surgical solution, considering the imminent risk of meningitis. The patient was also associated with the diagnosis of acute lithiasic cholecystitis. Results and discussions: The final chosen solution, right ventriculo-venous drainage using the cephalic vein, was a temporary surgical solution, but there are signs that this procedure can provide long-term ventricular drainage. Conclusions: Transcephalic ventriculo-subclavian drainage represents an alternative technical option, which can be used when established options become ineffective. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Brain Damage)

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