clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).

Background Clinical signs and their progression in Beagles with Lafora disease are poorly described. Objectives To describe clinical signs in Beagles with Lafora disease. Animals Twenty‐eight Beagles with Lafora disease confirmed by genetic testing or histopathology. Methods Retrospective multicenter case series. Data regarding signalment, clinical signs, diagnostic tests and treatment were retrieved from hospital data files. A questionnaire was sent to owners asking about neurological deficits, changes in cognitive functions, behavioral changes, response to treatment and survival time. Results Onset of clinical signs was 8.3 years (mean; range, 6.3‐13.3). All dogs had myoclonic episodes as an initial clinical sign with tonic‐clonic seizures in n = 11/28 (39%) and n = 12/28 (43%) later developing tonic‐clonic seizures. Deficits of coordination (n = 21/25; 84%), impaired vision (n = 15/26; 58%), and impaired hearing (n = 13/26; 50%) developed later. Mental decline was observed as loss of house training (urination; n = 8/25; 32%), difficulties performing learned tasks (n = 9/25; 36%), and difficulties learning new tasks (n = 7/23; 30%). Common behavioral changes were: increased photosensitivity (n = 20/26; 77%), staring into space (n = 16/25; 64%), reduced stress resistance (n = 15/26; 58%), increased noise sensitivity (n = 14/26; 54%), and separation anxiety (n = 11/25; 44%). Twenty‐one dogs were alive (median age 11.9 years; range, 9.8‐18.6), and 7 dogs were dead (mean age 12.1 years; SD: 1.3; range, 10.5‐12.6) at time of writing. Conclusions and Clinical Importance Lafora disease in Beagles causes significant behavioral changes, and mental decline as well as neurological deficits in addition to myoclonic episodes and generalized tonic‐clonic seizures. Nevertheless, a relatively normal life span can be expected.

Abstract. Borna disease (BD) is a fatal disorder of horses, often characterized by blindness. Although degeneration of retinal neurons has been demonstrated in a rat model, there are controversial data concerning whether a similar degeneration occurs in the retina of infected horses. To investigate whether BD may cause degeneration of photoreceptors and possibly of other neuronal cells at least at later stages of the disease, we performed a detailed quantitative morphologic study of retinal tissue from Borna-diseased horses. BD was diagnosed by detection of pathognomonic Joest-Degen inclusion bodies in the postmortem brains. Paraffin sections of paraformaldehyde-fixed retinae were used for histologic and immunohistochemical stainings. Numbers of neurons and Mü ller glial cells were counted, and neuron-to-Mü ller cell ratios were calculated. Among tissues from 9 horses with BD, we found retinae with strongly altered histologic appearance as well as retinae with only minor changes. The neuron-to-Mü ller cell ratio for the whole retina was significantly smaller in diseased animals (8.5 6 0.4; P , .01) as compared with controls (17.6 6 0.8). It can be concluded that BD in horses causes alterations of the retinal histology of a variable degree. The study provides new data about the pathogenesis of BD concerning the retina and demonstrates that a loss of photoreceptors may explain the observed blindness in infected horses.

BackgroundTreatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the ‘vigilance regulation model of mania’ which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania.Methods/designA multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression–Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-‘Vigilance Algorithm Leipzig’ (VIGALL).DiscussionA positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives.Trial registrationClinicalTrials.gov: NCT 01541605

The aim of the retrospective study was to describe the brain biopsy procedure using a new frameless optical neuronavigation system and to report diagnostic yield and complications associated with the procedure. Materials and MethOds:The medical records for all dogs with forebrain lesions that underwent brain biopsy with a frameless optical neuronavigation system in a single referral hospital between 2013 and 2020 were retrospectively analysed. Following data were collected: signalment, neurological signs, diagnostic findings, number of brain biopsy samples, sampled region, complications, duration of hospitalisation, whether the samples were diagnostic and histopathological diagnoses. The device consists of a computer workstation with navigation software, an infrared camera, patient tracker and reflective instruments. The biopsy needle was equipped with reflective spheres, so the surgeon could see the position of the needle during sampling the intracranial lesion free handed through a mini-burr hole.results: Ten dogs were included. Absolute diagnostic yield based on specific histopathological diagnosis was 73.9%. Three dogs had immune-mediated necrotizing encephalitis, two dogs showed a necrotizing leukoencephalitis and two dogs a meningoencephalitis of unknown origin. In two dogs, the brain specimen showed unspecific changes. In one dog, the samples were non-diagnostic. Seven dogs showed no neurological deterioration, one dog mild temporary ataxia and two dogs died within 36 hours post brain biopsy. clinical significance: In these 10 dogs, the frameless optical neuronavigation system employed was useful to gain diagnostic brain biopsy samples. Considering the mortality rate observed, further studies are needed to confirm the safety of this procedure and prove its actual clinical effectiveness.