Marco Rosati

AstraZeneca Computational Pathology

‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report th...

Intravascular lymphoma (IVL) is characterized by the proliferation of large malignant lymphocytes within the lumen of blood vessels. This retrospective, multi‐center, case series study aimed to describe the MRI features of confirmed central nervous system IVL in dogs and compare them with histopathological findings. Medical record databases from se...

A 9.5-year-old labrador presented with signs of progressive C1-C5 myelopathy. Magnetic resonance imaging of the cervical spine revealed a broad-based, jagged and partially ill-defined intradural mass lesion at the level of C3-C4 cervical vertebra. Decompressive spinal surgery was performed and the removed mass was sent for histopathological examina...

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 mas...

An 8-year-old female neutered Maltese Bichon Frise was presented to a small animal hospital for assessment of acute paraplegia. Diagnostic imaging including plain spinal radiographs and CT angiography was neither suggestive of an intervertebral disc extrusion nor any other abnormalities could be detected. The dog was referred to the emergency servi...

"Staggering disease" is a neurological disorder considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the dete...

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...

An 8‐year‐old female neutered Maltese Bichon Frise was presented to a small animal hospital for assessment of acute paraplegia. Diagnostic imaging including plain spinal radiographs and CT angiography was neither suggestive of an intervertebral disc extrusion nor any other abnormalities could be detected. The dog was referred to the emergency servi...

Gluten-related disorders in humans comprise different entities, including coeliac disease. Patients typically have measurable titers of anti-gliadin IgG or IgA (AGAs) and anti-transglutaminase-2 IgA (TG2). In addition to intestinal symptoms, human patients often show various neurological complications. In dogs, the neurological manifestation is rar...

Background: The endolymphatic sac is an organ devoid of sensory receptors. It is connected with the endolymphatic compartment and contains endolymph. Endolymphatic sac tumor (ELST) is a rare neoplasm involving the middle and inner ear described in humans and dogs that does not show cellular characteristics of malignancy, but can be locally invasive...

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 intramusc...

An 11‐week‐old male dachshund and its 13‐week‐old female sibling presented with slowly progressive gait abnormalities, cerebellar ataxia and intention head tremor. In the pedigree of their parents, there were no signs of these neurological abnormalities. The magnetic resonance imaging scan results, cerebrospinal fluid and complete blood analysis ob...

Background Granulomatous myositis is a rare condition in both humans and dogs. In humans it is most frequently related to sarcoidosis, where a concurrent granulomatous neuritis has been reported occasionally. Simultaneous granulomatous myositis and neuritis have been diagnosed previously in dogs (unpublished observations), but have not been studied...

We investigated the clinical, genetic, and pathological characteristics of a previously unknown severe juvenile brain disorder in several litters of Parson Russel Terriers. The disease started with epileptic seizures at 6–12 weeks of age and progressed rapidly to status epilepticus and death or euthanasia. Histopathological changes at autopsy were...

A nine‐year‐old female spayed Chihuahua dog had developed hypnic jerks and progressive myoclonic seizures three months before presentation. Neurological examination showed mental depression and spontaneous or reflex myoclonus. Magnetic resonance imaging findings were consistent with cerebral cortical atrophy and mild cranio‐cervical junction abnorm...

A 2‐year‐old Australian Shepherd dog was referred because of exercise intolerance and gait abnormalities. The dog had a history of idiopathic epilepsy treated with phenobarbitone and potassium bromide (KBr). The neurological examination was indicative of a generalized lower motor neuron disease. A generalized peripheral neuropathy caused by KBr was...

We investigated the clinical, genetic, and pathological characteristics of a previously unknown severe juvenile brain disorder in several litters of Parson Russel Terriers. The disease started with epileptic seizures at 6 to 12 weeks of age and progressed rapidly to status epilepticus and death or euthanasia. Histopathological changes at autopsy we...

Introduction of new imaging modalities for the equine brain have refocused attention on the horse as a natural model for ethological, neuroanatomical, and neuroscientific investigations. As opposed to imaging studies, strategies for equine neurodissection still lack a structured approach, standardization and reproducibility. In contrast to other sp...

Sporadic occurrence of juvenile-onset necrotizing encephalopathy (SNE) has been previously reported in Yorkshire terriers. However, so far, no causative genetic variant has been found for this breed-specific form of suspected mitochondrial encephalomyopathy. Affected dogs showed gait abnormalities, central visual defects, and/or seizures. Histopath...

Objective: Characterization of the etiology of meningoencephalitis and meningitis in dogs through an analysis of a veterinary hospital population. Material and methods: Retrospective study (2011-2016) with evaluation of clinical and diagnostic data of dogs with cerebrospinal fluid (CSF) pleocytosis (> 5/µl). Only dogs with cytological evaluation...

Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritanc...

A 7-year-old male entire vizsla, diagnosed with protein-losing nephropathy (PLN) one month previously, presented with lumbar hyperaesthesia. MRI of the lumbar spine revealed an extradural mass at the level of L3 vertebra. Most of the mass was surgically excised during left-sided pediculectomy at L3 and left-sided L2-L3 mini-hemilaminectomy. Histopa...

Background: Thoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs. Objectives: To further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy. Animals: Thirty client...

Systemic arterial hypertension represents a major risk factor for disruption of blood brain barrier and for vascular accidents in the adult central nervous system. To a certain extent, autoregulatory mechanisms of CNS vasculature shield the brain from hypertensive lesions by vasoconstriction and reduction of perfusion. Extensive and/or persistently...

After many years of controversy, there is now recent and solid evidence that classical Borna disease virus 1 (BoDV-1) can infect humans. On the basis of six brain autopsies, we provide the first systematic overview on BoDV-1 tissue distribution and the lesion pattern in fatal BoDV-1-induced encephalitis. All brains revealed a non-purulent, lymphocy...

Introduction: A new early-onset polyneuropathy has been increasingly recognized in related American Staffordshire Terriers across Europe. Clinical signs are stereotypic and comprise muscle atrophy, ataxia, decreased spinal reflexes, cutaneous hypoalgesia and laryngeal paralysis. Herein we describe the histopathologic features of this new familial p...

Case summary An 8-year-old spayed female domestic shorthair cat was referred for trismus of progressive onset, which had started at least 1 month previously. The patient presented with weakness, anorexia, chronic bilateral purulent nasal discharge and concurrent reduced nasal airflow. Upon physical examination, painful mouth opening, bilateral swel...

An 11-year-old spayed female dobermann was referred for progressive general proprioceptive ataxia and tetraparesis. MRI of the cervical spinal cord demonstrated a compressive, extradural, rounded space-occupying lesion at the C6-C7 right vertebral arch. The lesion was hypointense on T1-weighted images and hyperintense on T2-weighted images. The dog...

Background The only hereditary neurologic disorder described so far in American Staffordshire Terriers is adult‐onset cerebellar degeneration secondary to ceroid lipofuscinosis. We have seen several dogs with a newly recognized neurological disease characterized by locomotor weakness with or without respiratory signs and juvenile onset consistent w...

An eight-year-old, male intact, client-owned vaccinated Miniature Pinscher was admitted because of chronic progressive gait abnormality that appeared six months prior to referral. Neurological examination revealed a palmigrade stance, distal tetraparesis more severe to the thoracic limbs, a gait abnormality including hypermetria and laxity of both...

Introduction: The present case report describes the workup of unilateral fibular-nerve-paresis in a female neonatal Fleckvieh calf. The calf was admitted to the Clinic for Ruminants with Ambulatory and Herd Health Services, Ludwig- Maximilians-University Munich as part of an investigation into a herd problem. The herd problem was presented as move...

An eight week old Labrador Retriever puppy presented with stiff-legged robotic gait. Abnormal gait was most evident after rest and improved with prolonged activity. On occasions, initiation of sudden movements would result in collapse with rigidity of the trunk and stiff extended limbs for several seconds. Other clinical signs were excitement-induc...

Several enzymes are involved in fatty acid oxidation, which is a key process in mitochondrial energy production. Inherited defects affecting any step of fatty acid oxidation can result in clinical disease. We present here an extended family of German Hunting Terriers with 10 dogs affected by clinical signs of exercise induced weakness, muscle pain,...

Table S1. Data concerning individual dogs.

Table S2. Electrophysiology data concerning individual dogs.

Video S1 10 month‐old male AST with polyneuropathy. This dog had surgery 5 months earlier for laryngeal paralysis. Note the abnormal gait with tetraparesis and four limbs ataxia, palmigrade and plantigrade stances and pseudo hypermetria of the hock. Proprioceptive deficits are also displayed.

Video S2 13 month‐old female AST with advanced polyneuropathy. Note the respiratory distress with inspiratory dyspnoea, the tetraparesis and four limbs ataxia, the sensory deficits and the hyperextension of the limbs

The case study initially included over 20 patients presented during 2015-2017 with flaccid tetraparesis/tetraplegia. In all cases the initial tentative diagnosis was suspected Idiopathic Acute Polyradiculoneuritis (IAP) or Low Motor Neuron (LMN) disease of unknown aetiology The aim of this retrospective study is to report on the diagnostic investig...

The objective of this study was to describe the presence, prevalence, clinical manifestations, and risk factors of phantom complex and its effect on the quality of life for dogs that underwent amputation of a limb. An online questionnaire was developed containing 3 sections with a total of 69 questions. Clinical cases were recruited from a web site...

Feeding regimen (a), insulin treatment (b), and fasting blood glucose levels (c). Dots in panel c represent the mean fasting blood glucose level of the preceding week.

Quality assessment of RNA derived from various tissues of WT and MIDY pigs. RNA was extracted from heart, skeletal muscle, liver and kidney cortex of five WT and four MIDY pigs. As representative examples, the Agilent Bioanalyzer 2100 profiles obtained for two WT (736 and 738) and two MIDY (737 and 739) pigs are shown. For each sample the calculate...

Objective The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences of chronic insulin insufficiency and hyperglycemia, we established a comprehensive biobank of long-term diabetic INSC94Y transgenic pigs, a model of mutant INS gene-induced diabetes of youth (MIDY), and...

Acquired equine polyneuropathy (AEP), formerly also known as Scandinavian knuckling syndrome, is one of the most prevalent polyneuropathies in equids in Norway and Sweden, with more than 400 cases registered since first observations in 1995. Despite geographical clustering and an association to forage feeding, its aetiology remains unknown. Clinica...

Background: Immunohistochemical staining of entire nerve fibres allows for studying the molecular composition of functional fibre subunits and may add to the diagnostic value of nerve fibre teasing. New method: In this study, we established a sealed-slide method for reproducible immunostaining of deep axoplasmic proteins in permanently straighte...

Unter den fokalen Epilepsien der Katze (Felis silvestris catus) sticht die Temporallappenepilepsie (FTLE) durch charakteristische magnetresonanztomographische Veränderungen und das Auftreten orofazialer Automatismen hervor. Histopathologisch finden sich bei der FTLE am häufigsten entzündliche Infiltrate, im Sinne einer oft nekrotisierenden limbisch...

Cerebellar disorders in dogs can be subclassified into congenital, developmental and abiotrophic/degenerative types. Among the abiotrophies, the term cerebellar cortical degeneration (CCD) has been introduced lately, which includes an uncommon form mainly affecting granular cells. This variant has been described in several breeds including the Coto...

Recent views on Guillain-Barré syndrome (GBS) question the accuracy of classification into axonal and demyelinating subtypes that represent convergent neurophysiological phenotypes rather than immunological targets. Instead it has been proposed to clarify the primarily affected fibre subunit in nerve biopsies. As nerve biopsies rarely are part of r...

Clarification of central nervous system (CNS) disorders frequently requires pathological investigation via brain biopsy or postmortem examination. The use of cytology is usually restricted to diagnosis of mass lesions and septic meningitis. The value of brain cytology at postmortem examination has not been explored sufficiently. This study aimed to...

Case summary A 16-year-old neutered female domestic shorthair cat was referred for chronic history of reluctance to jump, stiffness of the tail and lower back pain. Mild pelvic limb ataxia, reduced perianal reflex and lumbosacral discomfort were present on neurological examination. On magnetic resonance imaging, a well-defined rounded structure of...

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete c...

Case summary A male neutered Ragdoll cat aged 11 years and 9 months presented with a 6 month history of weight loss and a 1 month history of lethargy and adipsia. A thorough clinical investigation confirmed a diagnosis of primary adipsia and hypernatraemia secondary to a non-secretory neuroendocrine pituitary macroadenoma. Relevance and novel info...

Hippocampal sclerosis (HS) refers to loss of hippocampal neurons and astrogliosis. In temporal lobe epilepsy (TLE), HS is a key factor for pharmacoresistance, even though the mechanisms are not quite understood. While experimental TLE models are available, there is lack of models reflecting the natural HS development. Amongst domestic animals, cats...

The voltage-gated calcium channel subunit α2δ plays a fundamental role in propagation of excitatory signals associated with release of glutamate and neuropeptides substance P (SP) and calcitonin gene-related protein (CGRP). It can be selectively inhibited by gabapentinoids. Hence, investigation of the α2δ subunit may predict the efficacy of gabapen...

Centronuclear myopathy (CNM) is an autosomal recessive hereditary disease affecting Labrador Retriever dogs. The disease is characterized by muscle lesions, typically encompassing reduction in the number and atrophy of type II fibers, and is caused by a short interspersed repeat element insertion in exon 2 of the protein tyrosine phosphatase-like m...