Repetitive transcranial magnetic stimulation (rTMS) has gained growing interest for the treatment of major depression (MDD) and treatment-resistant depression (TRD). Most knowledge on rTMS comes from ...human studies as preclinical application has been problematic. However, recent optimization of rTMS in animal models has laid the foundations for improved translational studies. Preclinical studies have the potential to help identify optimal stimulation protocols and shed light on new neurobiological-based rationales for rTMS use. To assess existing evidence regarding rTMS effects on depressive-like symptoms in rodent models, we conducted a comprehensive literature search in accordance with PRISMA guidelines (PROSPERO registration number: CRD42019157549). In addition, we conducted a meta-analysis to determine rTMS efficacy, performing subgroup analyses to examine the impact of different experimental models and neuromodulation parameters. Assessment of the depressive-like phenotype was quite homogeneous whilst rTMS parameters among the 23 included studies varied considerably. Most studies used a stress-induced model. Overall, results show a largely beneficial effect of active rTMS compared to sham stimulation, as reflected in the statistically significant recovery of both helplessness (SDM 1.34 1.02;1.66) and anhedonic (SDM 1.87 1.02;2.72) profiles. Improvement of the depressive-like phenotype was obtained in all included models and independently of rTMS frequency. Nonetheless, these results have limited predictive value for TRD patients as only antidepressant-sensitive models were used. Extending rTMS studies to other MDD models, corresponding to distinct endophenotypes, and to TRD models is therefore crucial to test rTMS efficacy and to develop cost-effective protocols, with the potential of yielding faster clinical responses in MDD and TRD.
Case summary A 4-year-old female spayed domestic shorthair cat was presented with facial swelling, ocular discharge and intermittent bilateral exophthalmos. Haematology revealed mild eosinophilia. ...Serum biochemistry showed a markedly elevated creatine kinase activity. MRI of the head revealed diffuse and severe changes of the masticatory muscles, including irregular areas compatible with fluid or necrosis within the abnormal muscle tissue. Cytological analysis of the left temporal muscle revealed eosinophilic and macrophagic inflammation. Bacterial and fungal cultures were negative. Serological titres against Toxoplasma gondii were compatible with previous exposure. A canine ELISA against masticatory muscle type IIM fibre proteins was positive at 1:4000 (reference interval <1:100). Histopathological examination of the left temporalis muscle revealed moderately severe and multifocal myositis. A diagnosis of immune-mediated masticatory myositis was made and immunosuppressive therapy was started. The cat initially responded to tapering doses of prednisolone, but subsequent relapses required therapy modulation. At the time of writing, 27 months after the initial diagnosis, the cat was in remission, but was diagnosed with diabetes mellitus, probably secondary to chronic glucocorticoid use. Relevance and novel information To our knowledge, this is the first case report to describe the MRI appearance of masticatory myositis in a cat and the second to describe the clinical presentation, histopathology, response to treatment and outcome in a cat with this condition.
Chronic kidney disease (CKD) is a renal dysfunction that can lead to high rates of mortality and morbidity, particularly when coupled with late diagnosis. CKD has become a major health problem due to ...its challenging detection at early stages when clear symptoms are yet to be presented. Thus, CKD is likely to be identified when the substantive conditions of the disease are manifest. In order to address the development of the disease and provide necessary treatments at the initial stage, the investigation of new biomarkers and metabolites associated with early detection of CKD are needed. Identified metabolites could be used to confirm the presence of the disease, obtain information on its mechanism and facilitate the development of novel pharmaceutical treatments. Such metabolites may be detected from biofluids and tissues using a range of analytical techniques. There are a number of metabolites that have been identified by mass spectrometry at high sensitivities, whilst the detection of metabolites directly from biofluids using NMR could present a more rapid way to expand our understanding of this disease. This review is focused on NMR-based metabolomics associated with CKD in humans and animals.
Case summary An 8-year-old neutered female domestic longhair cat was presented for investigation of a 48 h history of lethargy and pelvic limb ataxia. MRI of the spinal cord and vertebral column (C1 ...to sacrum) and brain was unremarkable. Lumbar cerebrospinal fluid analysis revealed pleocytosis and increased protein concentration. Thoracic radiographs and abdominal ultrasound were unremarkable. Anti-inflammatory doses of prednisolone were administered. Clinical deterioration occurred over the following 2 days, with the development of lower motor neuron deficits in both thoracic limbs. On repetition of the MRI, bilateral enlargement, T2-weighted hyperintensity, and marked contrast enhancement of the C7, C8 and T1 nerve roots, spinal nerves and brachial plexuses were observed. Infectious disease testing was negative. An immune-mediated inflammatory process was suspected and immunosuppressive doses of prednisolone were commenced. The clinical signs improved transiently, but marked deterioration occurred after 2 weeks. The patient was euthanased and a post-mortem examination was performed. A lymphocytic inflammatory infiltrate was detected in the C7, C8 and T1 nerve roots and dorsal root ganglia, and neoplastic plasma cells were identified in multiple organs. A diagnosis of non-cutaneous extramedullary plasmacytoma with multiorgan involvement and paraneoplastic ganglioradiculoneuritis was reached. Relevance and novel information Paraneoplastic ganglioradiculoneuritis in association with a plasma cell neoplasia has not been previously reported in the cat and should be considered as a differential diagnosis for cats with clinical or imaging evidence of an inflammatory process affecting the nerve roots, spinal nerves or brachial plexuses.
Gambling disorder (GD) is a behavioral addiction, in which dysfunctions in prefrontal activity have been proposed as relevant pathophysiological correlates. The aim of the present study was to ...preliminarily investigate the feasibility of a noninvasive neuromodulation intervention targeting the prefrontal cortex to treat GD in an open-label setting. We included 8 treatment-seeking patients with GD (7 males; 1 female; mean age: 40.6 ± 11.2). The study consisted of 3 phases: (1) outpatient screening phase, (2) 2-week intensive repetitive transcranial magnetic stimulation (rTMS) treatment phase (twice daily, 5 days/week for 2 weeks); and (3) 3-month maintenance follow-up phase (twice daily, once a week). Each high-frequency (15 Hz) rTMS session was delivered targeting the left dorsolateral prefrontal cortex. GD severity and treatment response were assessed at the baseline and during the follow-up. No relevant side effect was reported. We found a 71.2% Gambling Symptom Assessment Scale mean score reduction after 2 weeks of rTMS treatment; the days spent gambling decreased from 19.63 ± 7.96 to 0.13 ± 0.35 days. Clinical improvements were maintained throughout the study period. The lack of a control group limits the interpretation of these results. In conclusion, these results consolidate the rationale that rTMS interventions deserve further investigation as a potential treatment for GD. These protocols should be tested in larger randomized controlled studies, to determine the real benefits of neuromodulation in the clinical course of patients with GD. Registration Number: ClinicalTrials.gov Identifier NCT03336879.
Background
Congenital sensorineural deafness (CSD) is the most common type of deafness in Dalmatian dogs.
Objectives
To use results of CSD screening in Dalmatian dogs in the United Kingdom in genetic ...analysis and to determine any changes in the prevalence of CSD in this breed over time.
Animals
A total of 8955 Dalmatian puppies undergoing hearing function screening using brainstem auditory evoked response (BAER) between July 1992 and February 2019.
Methods
Results of BAER testing and pigmentation phenotypic data were linked to the UK Kennel Club Dalmatian pedigree database. Mixed model analysis was used to estimate variance parameters.
Results
The overall prevalence of CSD was 17.8% (13.4%, unilateral; 4.4%, bilateral). Heritability of CSD was approximately 0.3 (across models) and significantly >0. Genetic correlations between CSD and blue irises (+0.6) and pigmented head patch (−0.86) were large in magnitude and significantly different form 0. Significant improving phenotypic and genetic trends were identified, likely as the result of selection against deafness, equivalent to avoiding breeding with the 4% to 5% of animals with the highest genetic risk of CSD.
Conclusions and Clinical Importance
A decrease in the prevalence and genetic risk of CSD implies breeders have been selecting for hearing dogs. Selective breeding based on estimated breeding values (EBVs) can help further decrease the prevalence of CSD in Dalmatians in the future.
Vertebral lesions and associated neurological signs occur in dogs with multiple myeloma, however, veterinary literature describing MRI findings is currently lacking. The objective of this ...multicenter, retrospective, case series study was to describe neurological signs and MRI findings in a group of dogs that presented for spinal pain or other neurological deficits and had multiple myeloma. Electronic records of four veterinary referral hospitals were reviewed. Dogs were included if they had a pathologically confirmed diagnosis of multiple myeloma, had presented for spinal pain or other neurological signs, and had undergone MRI of the vertebral column. The MRI studies were evaluated and the anatomical location of lesion(s), signal intensity, presence of extra‐dural material, degree of spinal cord compression, extent of vertebral lesions, and contrast enhancement were recorded. Twelve dogs met inclusion criteria. Most dogs (n = 8) had a chronic progressive history, with varying degrees of proprioceptive ataxia and paresis (n = 11), and spinal pain was a feature in all dogs. The MRI findings were variable but more consistent features included the presence of multiple expansile vertebral lesions without extension beyond the outer cortical limits of affected vertebrae, and associated extradural material causing spinal cord compression. The majority of lesions were hyper‐ to isointense on T2 (n = 12) and T1‐weighted (n = 8) sequences, with variable but homogeneous contrast‐enhancement (n = 12). These described MRI characteristics of multiple myeloma may be used to aid early identification and guide subsequent confirmatory diagnostic steps, to ultimately improve therapeutic approach and long‐term outcome.
This review discusses terminology, pathological, clinical, and magnetic resonance imaging (MRI) findings, treatment, outcome, and prognostic factors of fibrocartilaginous embolic myelopathy (FCEM), ...acute non-compressive nucleus pulposus extrusion (ANNPE), and intradural/intramedullary intervertebral disk extrusion (IIVDE). FCEM, ANNPE, and IIVDE have a similar clinical presentation characterized by peracute onset of neurological dysfunction that is generally non-progressive after the initial 24-48 h. Differentiating between these conditions can be challenging, however, certain clinical and imaging findings can help. FCEM can occur in both adult and immature animals, whereas ANNPE or IIVDE have been reported only in animals older than 1 year. In dogs, ANNPE and IIVDE most commonly occur in the intervertebral disk spaces between T12 and L2, whereas FCEM has not such site predilection. In cats, FCEM occurs more frequently in the cervical spinal cord than in other locations. Data on cats with ANNPE and IIVDE are limited. Optimal MRI definition and experience in neuroimaging can help identify the findings that allow differentiation between FCEM, ANNPE, and IIVDE. In animals with ANNPE and IIVDE, the affected intervertebral disk space is often narrowed and the focal area of intramedullary hyperintensity on T2-weighted images is located above the affected intervertebral disk space. In dogs with ANNPE signal changes associated with the extruded nucleus pulposus and epidural fat disruption can be identified in the epidural space dorsal to the affected intervertebral disk. Identification of a linear tract (predominantly hyperintense on T2-weighted images, iso to hypointense on T1-weighted images and hypointense on T2*-weighted gradient recall echo images) extending from the intervertebral disk into the spinal cord parenchyma is highly suggestive of IIVDE. Treatment of FCEM and ANNPE is conservative. Dogs reported with IIVDE have been managed either conservatively or surgically. Prognostic factors include degree of neurological dysfunction (particularly loss of nociception) and disease-specific MRI variables.
Spinocerebellar ataxia in the Italian Spinone dog breed is characterised by a progressive gait abnormality that manifests from approximately 4 months of age. The disorder shows an autosomal recessive ...mode of inheritance, and affected individuals are usually euthanized by one year of age on welfare grounds due to an inability to ambulate. Using a homozygosity mapping technique with six cases and six controls, we mapped the disease locus to chromosome 20 of the canine genome. Linkage analysis across an extended pedigree confirmed the association, with microsatellite C20.374 achieving a maximal LOD score of 4.41. All five genes within the disease-associated interval were exon resequenced, although no exonic candidate mutations were identified. A targeted resequencing approach was therefore adopted to sequence the entire disease-associated interval. Analysis of the sequencing data revealed a GAA repeat expansion in intron 35 of ITPR1, which was homozygous in all cases and heterozygous in obligate carriers. Partial impairment of cerebellar ITPR1 expression in affected dogs was demonstrated by immunohistochemistry. Given the association of ITPR1 mutations with spinocerebellar ataxia (SCA) type 15 (also designated SCA16) in humans and that an intronic GAA repeat expansion has been shown to cause Friedreich ataxia, the repeat expansion is an excellent candidate for the cause of spinocerebellar ataxia in the Italian Spinone. This finding represents the first naturally occurring pathogenic intronic GAA repeat expansion in a non-human species and a novel mechanism for ITPR1 associated spinocerebellar ataxia.
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