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Abstract Background Autoimmune mechanisms represent a novel category for causes of seizures and epilepsies in humans, and LGI1‐antibody associated limbic encephalitis occurs in cats. Hypothesis/Objectives To investigate the presence of neural antibodies in dogs with epilepsy or dyskinesia of unknown cause using human and murine assays modified for use in dogs. Animals Fifty‐eight dogs with epilepsy of unknown cause or suspected dyskinesia and 57 control dogs. Methods Serum and CSF samples were collected prospectively as part of the diagnostic work‐up. Clinical data including onset and seizure/episode type were retrieved from the medical records. Screening for neural antibodies was done with cell‐based assays transfected with human genes for typical autoimmune encephalitis antigens and tissue‐based immunofluorescence assays on mouse hippocampus slices in serum and CSF samples from affected dogs and controls. The commercial human und murine assays were modified with canine‐specific secondary antibody. Positive controls were from human samples. Results The commercial assays used in this study did not provide unequivocal evidence for presence of neural antibodies in dogs including one dog with histopathologically proven limbic encephalitis. Low titer IgLON5 antibodies were present in serum from one dog from the epilepsy/dyskinesia group and in one dog from the control group. Conclusion and Clinical Importance Specific neural antibodies were not detected using mouse and human target antigens in dogs with epilepsy and dyskinesia of unknown origin. These findings emphasize the need for canine‐specific assays and the importance of control groups.

Rustrela virus (RusV) was detected in the brains of 27 out of 29 domestic cats with ‘staggering disease’, but not of 29 control cats. This suggests RusV as the long-sought causative agent of ‘staggering disease’, which had been obscure for 50 years.

Abstract Background Increased cerebrospinal fluid (CSF) protein concentration is a common finding in neurological diseases of dogs. Distinguishing between intrathecally‐produced proteins and proteins that have passed the blood‐CSF barrier because of barrier disruption facilitates diagnosis. Albumin is a microprotein mainly produced extrathecally that can be used as a reference marker for blood‐CSF barrier dysfunction. Objectives Develop a quotient graph based on the CSF/serum quotient of albumin and immunoglobulin A (IgA; Reibergram) to visualize intrathecal IgA synthesis and blood‐CSF barrier dysfunction. Animals and Methods Retrospective single‐center cohort study. A hyperbolic function was developed using data from 6 healthy Beagles and 38 dogs with neurological diseases in which an isolated blood‐CSF barrier dysfunction was expected. The function was validated using data from 10 dogs with expected intrathecal IgA synthesis and was visualized as a quotient graph. Finally, the graph was used to evaluate data of 118 dogs with various neurological diseases. Results Within the Reibergram, the function QLimIgA=0.13QAlb2+11.9·10−6−1.01·10−3 describes the upper values of physiological IgA quotients. It detects diseases with expected intrathecal IgA synthesis with higher sensitivity (85%) and specificity (89%) than the IgA index. The upper value of the physiological albumin quotient is 2.22 and detects diseases with expected blood‐CSF barrier dysfunction (sensitivity: 81%; specificity: 88%). Conclusion and Clinical Importance The canine Reibergram can detect blood‐CSF barrier dysfunction and intrathecal IgA synthesis in the majority of cases. The graphical visualization simplifies data evaluation and makes it a feasible tool in routine CSF diagnostic testing.

Abstract Background Specialized neurons in the diencephalon detect blood hypernatremia in dehydrated animals. These neurons are connected with the pituitary gland, subsequently producing antidiuretic hormone to reabsorb water from urine in the kidneys, and to the forebrain to generate thirst and trigger drinking behavior. Case presentation This is the first case report describing clinical findings, magnetic resonance imaging (MRI) and necropsy results of a Belted Galloway heifer with severe clinical signs of dehydration and hypernatremia, but concurrent adipsia and isosthenuria. Due to insufficient recovery with symptomatic treatment, owners elected euthanasia. Postmortem MRI and necropsy revealed a complex forebrain malformation: mild abnormal gyrification of the forebrain cortex, lobar holoprosencephaly, and corpus callosum hypoplasia. The affected brain structures are well known to be involved in osmoregulation and generation of thirst in dogs, humans and rodents. Conclusions Complex forebrain malformation can be involved in the pathogenesis of hypernatremia and adipsia in bovines.

Steroid-responsive meningitis-arteritis (SRMA) is a predominantly Th-2 immune-mediated disease, but the exact pathomechanism remains unclear. Interleukin-31 (IL-31) is predominantly produced by T cells with a Th-2 phenotype during proinflammatory conditions. We hypothesize that IL-31 might be involved in the pathogenesis of SRMA. IL-31 was measured in archived samples (49 serum and 52 CSF samples) of dogs with SRMA, meningoencephalitis of unknown origin (MUO), infectious meningoencephalitis, and atopic dermatitis, and of healthy control dogs using a competitive canine IL-31 ELISA. The mean serum IL-31 level in dogs with SRMA (n = 18) was mildly higher compared to dogs with atopic dermatitis (n = 3, p = 0.8135) and MUO (n = 15, p = 0.7618) and markedly higher than in healthy controls (n = 10, p = 0.1327) and dogs with infectious meningoencephalitis (n = 3, no statistics). Dogs with SRMA in the acute stage of the disease and without any pre-treatment had the highest IL-31 levels. The mean CSF IL-31 value for dogs with SRMA (n = 23) was quite similar to that for healthy controls (n = 8, p = 0.4454) and did not differ markedly from dogs with MUO (n = 19, p = 0.8724) and infectious meningoencephalitis. Based on this study, an involvement of IL-31 in the pathogenesis of the systemic Th-2 immune-mediated immune response in SRMA can be assumed as a further component leading to an aberrant immune reaction.

A male 10-year-old captive red kangaroo (Macropus rufus) was presented with a chronic progressive pelvic limb lameness and reluctance to jump. The general examination revealed a palpable induration of the lumbar epaxial muscles. Magnetic resonance imaging performed under general anesthesia revealed bilateral almost symmetric, well-circumscribed mass lesions in superficial erector spinae muscles. The lesions had irregular to multilobulated appearance with hyper-, hypo-, and isointense areas in T2- and T1-weighted (w) sequences without contrast enhancement. On computed tomography, a peripheral rim of mineralization was apparent. Histopathological analysis of a muscle biopsy showed osseous trabeculae with rare clusters of chondrocytes indicating metaplasia of muscle tissue to bone. No indications of inflammation or malignancy were visible. The clinical, histopathological, and imaging workup of this case was consistent with myositis ossificans circumscripta. This disorder is particularly well-known among human professional athletes such as basketball players, where excessive, chronic-repetitive force or blunt trauma causes microtrauma to the musculature. Metaplasia of muscle tissue due to abnormal regeneration processes causes heterotopic ossification. The kangaroo's clinical signs improved with cyto-reductive surgery, cage rest, weight reduction, and meloxicam without further relapse.

Inflammatory polyradiculoneuropathy (IMPN) is one of the causes of sudden onset of neuromuscular signs such as para-/tetraparesis in young cats. Even though most cases have a favorable outcome, persistent deficits, relapses, and progressive courses are occasionally seen. As clinical presentation does not always appear to predict outcome and risk of recurrence, this study was initiated to screen for prognostic biopsy findings in a large cohort of histologically confirmed IMPN cases with clinical follow-up. In total, nerve and muscle specimens of 107 cats with biopsy diagnosis of presumed autoreactive inflammatory polyneuropathy and 22 control cases were reviewed by two blinded raters for a set of 36 histological parameters. To identify patterns and subtypes of IMPN, hierarchical k-means clustering of 33 histologic variables was performed. Then, the impact of histological parameters on IMPN outcome was evaluated via an univariate analysis to identify variables for the final multivariate model. The data on immediate outcome and follow-up were collected from submitting neurologists using a purpose-designed questionnaire. Hierarchical k-means clustering sorted the tissues into 4 main categories: cluster 1 (44/129) represents a purely inflammatory IMPN picture, whereas cluster 2 (47/129) was accompanied by demyelinating features and cluster 3 (16/129) by Wallerian degeneration. Cluster 4 (22/129) reflects normal tissues from non-neuropathic control cats. Returned questionnaires provided detailed information on outcome in 63 animals. They were categorized into recovered and non-recovered. Thereby, fiber-invasive infiltrates by mononuclear cells and mild fiber loss in intramuscular nerve branches correlated with higher probabilities of recovery. Remyelination in semithin sections, on the other hand, is correlated with a less favorable outcome. Animals grouping in cluster 1 had a tendency to a higher probability of recovery compared to other clusters. In conclusion, diagnosis of feline IMPN from nerve and muscle biopsies allowed for the identification of histologic features that were positively or negatively correlated with outcome.

Abstract Background Because of fast leucocyte degeneration in cerebrospinal fluid (CSF) laboratory examinations of CSF samples should be performed approximately within 30 min after withdrawal. This study examines the storage of canine and feline CSF samples in “TransFix®/EDTA CSF Sample Storage Tubes” (Cytomark, Buckingham, UK) for preventing leucocytes from degeneration, so that routine and flow cytometry examinations are feasible up to 3 days after sampling. Results After storage in TransFix® tubes, leukocytes could not be adequately stained with Türk’s solution and differentiating between erythrocytes and leukocytes was cumbersome. In addition, the cell morphology could not be sufficiently assessed on cytospin preparations because of shrunken leukocytes and indistinct cell nuclei. In contrast, by flow cytometry, a significantly higher cell count was measured over the entire study period in the samples stored in TransFix® tubes compared to the untreated samples. The antibodies (AB) against CD3, CD4 and CD21, against CD11b and against CD45 showed a good binding strength and thus enabled a good differentiation of cell populations. However, after storage in the TransFix® tubes, monocytes were no longer detectable using an AB against CD14. Conclusion Based on these results, “TransFix®/EDTA CSF Sample Storage Tubes” can be used for extended storage prior to flow cytometric analysis of lymphocytes and granulocytes in CSF samples but not for detecting monocytes. However, standard examinations, such as microscopic cell counting and morphological cell assessment should be performed on fresh CSF samples.

Extracellular traps (ETs) are DNA networks formed by immune cells to fight infectious diseases by catching and attacking pathogenic microorganisms. Uncontrolled ET formation or impaired ET clearance can cause tissue and organ damage. Steroid-responsive meningitis-arteritis (SRMA) represents an immune-mediated, presumably non-infectious, purulent leptomeningitis and fibrinoid-necrotizing arteritis and periarteritis of young-adult dogs. Chronic and recurrent cases of SRMA are characterized by lymphohistiocytic inflammatory cell infiltration in the meninges and perivascular tissue. This study aimed to identify extracellular traps in dogs with SRMA, a model for immune-mediated diseases in the central nervous system (CNS). Hematoxylin and eosin-stained samples of two young dogs with chronic, recurrent SRMA were examined by light microscopy for characteristic lesions and consecutive slices of affected tissues were stained for detection of ETs by immunofluorescence microscopy using antibodies against DNA–histone-1 complexes, myeloperoxidase, and citrullinated histone H3. Histology revealed purulent and lymphohistiocytic leptomeningitis (n = 2/2) with meningeal periarteritis (n = 2/2) and periadrenal located lymphohistiocytic periarteritis (n = 1). Extracellular DNA networks and inflammatory cell infiltrates of macrophages, neutrophil granulocytes, and lymphocytes were detected in the subarachnoid space of the leptomeninx (n = 2/2) and perivascularly in meningeal (n = 2/2) as well as periadrenal vessels (n = 1/1). In summary, extracellular DNA fibers and attached ET markers are detectable in affected perivascular and meningeal tissues of dogs suffering from SRMA. The proof of principle could be confirmed that ETs are present in canine, inflammatory, and non-infectious CNS diseases and possibly play a role in the pathogenesis of SRMA.

There is a paucity of information on the clinical course and outcome of young cats with polyneuropathy. The aim of the study was to describe the clinical features, diagnostic investigations, and outcome of a large cohort of cats with inflammatory polyneuropathy from several European countries. Seventy cats with inflammatory infiltrates in intramuscular nerves and/or peripheral nerve biopsies were retrospectively included. Information from medical records and follow up were acquired via questionnaires filled by veterinary neurologists who had submitted muscle and nerve biopsies (2011–2019). Median age at onset was 10 months (range: 4–120 months). The most common breed was British short hair (25.7%), followed by Domestic short hair (24.3%), Bengal cat (11.4%), Maine Coon (8.6%) and Persian cat (5.7%), and 14 other breeds. Male cats were predominantly affected (64.3%). Clinical signs were weakness (98.6%) and tetraparesis (75.7%) in association with decreased withdrawal reflexes (83.6%) and, less commonly, cranial nerve signs (17.1%), spinal pain/hyperesthesia (12.9%), and micturition/defecation problems (14.3%). Onset was sudden (30.1%) or insidious (69.1%), and an initial progressive phase was reported in 74.3%. Characteristic findings on electrodiagnostic examination were presence of generalized spontaneous electric muscle activity (89.6%), decreased motor nerve conduction velocity (52.3%), abnormal F-wave studies (72.4%), pattern of temporal dispersion (26.1%) and unremarkable sensory tests. The clinical course was mainly described as remittent (49.2%) or remittent-relapsing (34.9%), while stagnation, progressive course or waxing and waning were less frequently reported. Relapses were common and occurred in 35.7% of the cats' population. An overall favorable outcome was reported in 79.4% of patients. In conclusion, young age at the time of diagnosis and sudden onset of clinical signs were significantly associated with recovery (p < 0.05). Clinical and electrodiagnostic features and the remittent-relapsing clinical course resembles juvenile chronic inflammatory demyelinating polyneuropathy (CIDP), as seen in human (children/adolescents), in many aspects.

Abstract Background Munchkin cats were founded on a naturally occurring mutation segregating into long-legged and short-legged types. Short-legged cats showed disproportionate dwarfism (chondrodysplasia) in which all four legs are short and are referred as standard Munchkin cats. Long-legged animals are referred as non-standard Munchkin cats. A previous study using genome-wide single nucleotide polymorphisms (SNPs) for genome-wide association analysis identified a significantly associated region at 168–184 Mb on feline chromosome (FCA) B1. Results In this study, we validated the critical region on FCA B1 using a case-control study with 89 cats and 14 FCA B1-SNPs. A structural variant within UGDH (NC_018726.2:g.173294289_173297592delins108, Felis catus 8.0, equivalent to NC_018726.3:g.174882895_174886198delins108, Felis catus 9.0) on FCA B1 was perfectly associated with the phenotype of short-legged standard Munchkin cats. Conclusion This UGDH structural variant very likely causes the chondrodysplastic (standard) phenotype in Munchkin cats. The lack of homozygous mutant phenotypes and reduced litter sizes in standard Munchkin cats suggest an autosomal recessive lethal trait in the homozygote state. We propose an autosomal dominant mode of inheritance for the chondrodysplastic condition in Munchkin cats.

Abstract Background In dogs, meningiomas mostly cause chronic progressive clinical signs due to slow tumor growth. Case presentation In contrast, three dogs were presented with the history of chronic generalized tonic-clonic seizures and peracute deterioration with sudden onset of neurological deficits in accordance with an extensive unilateral forebrain lesion. Magnetic resonance imaging examinations of the dogs revealed a well-delineated extraaxial T2W hyperintense mass in the rostral forebrain with homogeneous contrast enhancement. Additionally, an intraaxial, well-demarcated, unilateral lesion was apparent in the parenchyma supplied by the middle cerebral artery. In two cases, necropsy revealed meningothelial meningioma in the rostral fossa and marked eosinophilic neuronal necrosis, a sign of ischemia, focal malacia, edema and gliosis in the temporal lobe and hippocampus because of a focal thrombosis of the middle cerebral artery. In the third case symptomatic treatment resulted in improvement of clinical signs enabling a good quality of life for the patient. Conclusions In dogs with structural epilepsy caused by meningioma, acute deterioration of clinical signs can be associated with ischemic infarctions as a potential complication.

Case-based learning is a valuable tool to impart various problem-solving skills in veterinary education and stimulate active learning. Students can solve imaginary cases without the need for contact with real patients. Case-based teaching can be well performed as asynchronous remote-online class. In time of the COVID-19-pandemic, many courses in veterinary education are provided online. Therefore, students report certain fatigue when it comes to desk-based online learning. The app “Actionbound” provides a platform to design digitally interactive scavenger hunts based on global positioning system (GPS)—called “bounds” —in which the teacher can create a case study with an authentic patient via narrative elements. This app was designed for multimedia-guided museum or city tours initially. The app offers the opportunity to send the students to different geographic localizations for example in a park or locations on the University campus, like geocaching. In this way, students can walk outdoors while solving the case study. The present article describes the first experience with Actionbound as a tool for mobile game-based and case-orientated learning in veterinary education. Three veterinary neurology cases were designed as bounds for undergraduate students. In the summer term 2020, 42 students from the second to the fourth year of the University of Veterinary Medicine Hannover worked on these three cases, which were solved 88 times in total: Cases 1 and 2 were each played 30 times, and case 3 was played 28 times. Forty-seven bounds were solved from students walking through the forest with GPS, and 41 were managed indoors. After each bound, students evaluated the app and the course via a 6-point numerical Likert rating scale (1 = excellent to 6 = unsatisfactory). Students playing the bounds outdoors performed significantly better than students solving the corresponding bound at home in two of the three cases (p = 0.01). The large majority of the students rated the course as excellent to good (median 1.35, range 1–4) and would recommend the course to friends (median 1.26, range 1–3). Summarizing, in teaching veterinary neurology Actionbound's game-based character in the context of outdoor activity motivates students, might improve learning, and is highly suitable for case-based learning.

Abstract Background The split spinal cord malformation (SSCM) is an uncommon congenital malformation of the vertebral canal in which parts of the spinal cord are longitudinally duplicated. In SSCM Type I, each spinal cord has its own dura tube. In the SSCM Type II, both parts of the spinal cord are surrounded by a common dura tube. Cases presentation During the clinical examination one calf showed ambulatory paresis and 3 calves non-ambulatory paraparesis. Calf 4 additionally had a congenital tremor. The examination of calf 4 using magnetic resonance imaging (MRI) showed a median hydrosyringomyelia at the level of the 4th lumbar vertebra. The caudal part of this liquid-filled cavity was split longitudinally through a thin septum. From there, the spinal cord structures duplicated with an incomplete division, so that the transverse section of the spinal cord appeared peanut-shaped and in each half a central canal could be observed. The pathological-anatomical examination after euthanasia showed a duplication of the spinal cord in the area of the lumbar vertebral column in all calves. The histopathological examination revealed two central lumbar vertebral column channels. The two spinal cord duplicates were each surrounded by two separate meninges in calf 2 (SSCM type I); in the other calves (1, 3, 4, and) the two central canals and the spinal cord were covered by a common meninx (SSCM type II). A pedigree analysis of calves 2, 3 and 4 showed a degree of relationship suggestive of a hereditary component. This supports the hypothesis of a possible recessive inheritance due to common ancestors, leading to partial genetic homozygosity. Conclusions The clinical appearance of SSCM can vary widely. In calves with congenital paralysis SSCM should always be considered as a differential diagnosis. A reliable diagnosis intra vitam is possible only with laborious imaging procedures such as MRI. Further studies on the heritability of this malformation are necessary to confirm a genetic cause of this disease.

Sudden unexpected death in human epileptic patients (SUDEP) is defined as death related to recurrent unprovoked seizures, death occurring unexpectedly, and suddenly in a patient with reasonable state of health, without an obvious medical cause of death, trauma, asphyxia, or intractable status epilepticus, and in post mortem examination no obvious reason for death can be found. “Probable SUDEP” (pSUDEP) is defined as SUDEP not confirmed pathologically. The adapted abbreviation for dogs is used in the following: “pSUDED” (probable sudden unexpected death in dogs with epilepsy). The aim of the present monocentric retrospective study using an online questionnaire was to evaluate the occurrence of pSUDED. Data of canine patients presented with seizures between 01/1998 and 05/2018 were retrospectively analyzed and classified according to their etiology (n = 1,503). Owners were contacted by telephone to participate in answering a validated questionnaire. A total of 509 owners were reached, and 373 owners completed the questionnaire. In addition to signalement (e.g., breed), special attention was paid to the frequency and presentation of seizures and seizures in the context of death. Fifty-one percent (191/373) of the dogs were dead at the endpoint of the study. A large proportion of the dogs was euthanized (149/191) because of seizure severity or health problems unrelated to seizures. Idiopathic epilepsy (IE) was diagnosed in 19/34 dogs which died unexpectedly. Of these seven animals had to be excluded for further investigation of pSUDED because of status epilepticus or aspiration pneumonia as a result of the seizures. In 12 dogs with IE the last seizure event occurred between 6 h and ~3 months before death. pSUDED was suspected in these dogs and an occurrence rate of 4.5–10% was calculated. pSUDED appears in a similar occurrence rate as human SUDEP and should be considered as a possible complication in epileptic dogs. The results of this study suggest that dogs with IE but especially those with brachycephalic syndrome and cluster seizures have an increased risk to die of pSUDED. Owners of dogs with seizures should be educated about the risk of sudden death in dogs with epilepsy.

Meningoencephalomyelitis of unknown origin (MUO) is an umbrella term describing inflammatory changes of the central nervous system (CNS) with suspected non-infectious etiology. Diagnosis of MUO mostly remains presumed in a clinical setting. Histopathological and immunohistochemical examination of CNS tissue represent additional tools for detection of inflammation and the exclusion of specific infectious agents. While MUO is well-described in canine patients, only little is known about MUO in cats. Previous reports of feline MUO involve either clinical findings or histopathological examination but not both. The present case series is the first report describing both clinical and histopathological findings of feline MUO: Four cats (age: 1.7–17.8 years) showed acute to chronic progressive neurological signs of encephalopathy or myelopathy. Three cats had extraneural signs (hyperthermia, weight loss, hyporexia, leukocytosis). Magnetic resonance imaging (MRI) showed multifocal intraparenchymal lesions in forebrain, brainstem or spinal cord with homogenous contrast enhancement (2/2). Cerebrospinal fluid (CSF) examination was normal or displayed albuminocytologic dissociation. Histopathology revealed a multifocal, lympho-histiocytic meningoencephalitis in three cases and a lympho-histiocytic myelitis in one case. Immunohistochemistry for feline parvovirus, feline coronavirus, feline herpesvirus, tick borne encephalitis virus, Borna disease virus, morbillivirus, rabies virus, suid herpesvirus-1, and Toxoplasma gondii were negative in all cases.One Sentence SummaryThis case series is the first one reporting both clinical and histopathological findings in cats with MUO. Feline MUO incorporates heterogeneous subtypes of sterile CNS inflammation.

We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventral strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in the centrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal reduction of myelin formation and moderate diffuse edema without inflammation was detected leading to the diagnosis of leukodystrophy. Combined linkage analysis and homozygosity mapping in two related families delineated critical intervals of approximately 29 Mb. The comparison of whole genome sequence data of one affected Standard Schnauzer to 221 control genomes revealed a single private homozygous protein changing variant in the critical intervals, TSEN54:c.371G>A or p.(Gly124Asp). TSEN54 encodes the tRNA splicing endonuclease subunit 54. In humans, several variants in TSEN54 were reported to cause different types of pontocerebellar hypoplasia. The genotypes at the c.371G>A variant were perfectly associated with the leukodystrophy phenotype in 12 affected Standard Schnauzers and almost 1000 control dogs from different breeds. These results suggest that TSEN54:c.371G>A causes the leukodystrophy. The identification of a candidate causative variant enables genetic testing so that the unintentional breeding of affected Standard Schnauzers can be avoided in the future. Our findings extend the known genotype-phenotype correlation for TSEN54 variants.

For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.