Cultivation of Schwann cells from fresh and non-fresh adult equine peripheral nerves.

BACKGROUND: Over the past 25 years, acquired equine polyneuropathy (AEP) has emerged as a neurological disease in Scandinavian horses. This condition is characterized by histopathological features including the presence of Schwann cell (SC) inclusions. Cultivated equine SCs would serve as a valuable resource for investigations of factors triggering this Schwannopathy. Ideally, cells should be sampled for cultivation from fresh nerves immediately after death of the animal, however the availability of fresh material is limited, due to the inconsistent case load and the inherent technical and practical challenges to collection of samples in the field. This study aimed to cultivate SCs from adult equine peripheral nerves and assess their ability to survive in sampled nerve material over time to simulate harvesting of SCs in field situations. NEW METHODS: Peripheral nerves from five non-neurological horses were used. After euthanasia, both fresh and non-fresh nerve samples were harvested from each horse. Flow cytometry was employed to confirm the cellular identity and to determine the SC purity. RESULTS: The results revealed successful establishment of SC cultures from adult equine peripheral nerves, with the potential to achieve high SC purity from both fresh and non-fresh nerve samples. COMPARISON WITH EXISTING METHOD: While most SC isolation methods focus on harvest of cells from fresh nerve materials from laboratory animals, our approach highlights the possibility of utilizing SC cultures from field-harvested and transported nerve samples from horses. CONCLUSIONS: We describe a method for isolating SCs with high purity from both fresh and non-fresh peripheral nerves of adult horses.

Mutations in the CYP27B1 gene cause vitamin D dependent rickets in pugs.

Rickets is a disorder of bone development and can be the result of either dietary or genetic causes. Here, related pugs from 2 litters were included. Three pugs had clinical signs including, lameness, bone deformities, and dyspnea. One other pug was found dead. Radiographs of 2 affected pugs, 5 and 6 months old, showed generalized widening, and irregular margination of the physes of both the appendicular and the axial skeleton with generalized decrease in bone opacity and bulbous swelling of the costochondral junctions. Two pugs had low serum calcium and 1,25 (OH)2 D3 concentrations. Test results further indicated secondary hyperparathyroidism with adequate concentrations of 25-hydroxyvitamin D. Necropsy revealed tongue-like projections of cartilage extending into the metaphysis consistent with rickets, loss of metaphyseal mineralization and lung pathology. Vitamin D-dependent rickets was diagnosed. A truncating mutation in the 1α-hydroxylase gene (CYP27B1) was identified by genome sequence analysis of the pugs with VDDR type 1A. Vitamin D-dependent rickets type 1A can occur in young pugs, and if left untreated is a life-threatening condition. Early medical intervention can reverse clinical signs and should be instituted as soon as possible.

A 1 bp deletion in HACE1 causes ataxia in Norwegian elkhound, black.

A number of inherited ataxias is known in humans, with more than 250 loci implicated, most of which are included in human ataxia screening panels. Anecdotally, cases of ataxia in the Norwegian elkhound black have been known for the last 40 years. Affected puppies from three litters were clinically and neurologically examined, and postmortem samples were collected for morphological studies, including ultrastructural analyses. The puppies displayed vestibulocerebellar neurological signs and had degenerative histopathological alterations in cerebellum and brain stem. Three affected dogs, each from different litters, as well as both parents and one healthy littermate from each litter, were whole genome sequenced. Through variant calling we discovered a disease-associated 1 bp deletion in HACE1 (CFA12), resulting in a frameshift at codon 333 and a premature stop codon at codon 366. The perfect association combined with the predicted significant molecular effect, strongly suggest that we have found the causative mutation for Norwegian elkhound black ataxia. We have identified a novel candidate gene for ataxia where dogs can serve as a spontaneous model for improved understanding of ataxia, also in human.

Granulomatous interstitial polymyositis and intramuscular neuritis in a dog.

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 further. Additional investigations are therefore warranted to characterize this disorder. Here we present a detailed description of concurrent idiopathic granulomatous myositis and granulomatous neuritis in a dog with suspected immune-mediated aetiology. CASE PRESENTATION: The dog presented with dysphonia and paresis in the pelvic limbs and tail. In addition to muscle biopsies being taken for histopathology, magnetic resonance imaging, computed tomography and electrodiagnostics were performed. Muscle biopsies displayed granuloma formation with giant cells and epithelioid macrophages in muscle fibres and nerve branches. Microorganisms were not detected. Long-term treatment with glucocorticoids was clinically successful. Two years after the clinical signs started, the dog presented with signs of sepsis and died. Histopathologically, no granulomatous inflammation could be demonstrated in either muscles or nerves at that time. CONCLUSIONS: This case illustrates a granulomatous interstitial polymyositis and intramuscular neuritis that improved clinically and resolved histologically with glucocorticoid treatment. Idiopathic granulomatous myositis and neuritis should be considered as a differential diagnosis in dogs with clinical signs of neuromuscular disorders.

Thoracolumbar meningeal fibrosis in pugs.

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-owned pure-bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study. METHODS: Prospective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death. RESULTS: Twenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66-96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho-histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs. CONCLUSIONS AND CLINICAL IMPORTANCE: Meningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long-standing thoracolumbar myelopathy.

High prevalence of gait abnormalities in pugs.

The objective of this prospective study was to determine the prevalence of gait abnormalities in a cohort of Swedish pugs by using an owner-based questionnaire targeting signs of gait abnormality and video footage showing the dog's gait. This study also evaluated associated conditions of abnormal gait, including other health disorders prevalent in the breed. Five hundred and fifty (550) pugs registered in the Swedish Kennel Club, of one, five and eight years of age, in 2015 and 2016, were included in the study. Gait abnormalities were reported in 30.7 per cent of the responses. In the majority of cases, the character of the described gait indicated a neurological cause for the gait abnormality. An association was observed between abnormal gait and age, with gait abnormalities being significantly more common in older pugs (P=0.004). An association was also found between abnormal gait and dyspnoea, with dyspnoea being significantly more common in pugs with gait abnormalities (P<0.0001). This study demonstrated that the prevalence of gait abnormalities was high in the Swedish pug breed and increased with age. Future studies on the mechanisms behind these gait abnormalities are warranted.

Basal Autophagy Is Altered in Lagotto Romagnolo Dogs with an ATG4D Mutation.

A missense variant in the autophagy-related ATG4D-gene has been associated with a progressive degenerative neurological disease in Lagotto Romagnolo (LR) dogs. In addition to neural lesions, affected dogs show an extraneural histopathological phenotype characterized by severe cytoplasmic vacuolization, a finding not previously linked with disturbed autophagy in animals. Here we aimed at testing the hypothesis that autophagy is altered in the affected dogs, at reporting the histopathology of extraneural tissues and at excluding lysosomal storage diseases. Basal and starvation-induced autophagy were monitored by Western blotting and immunofluorescence of microtubule associated protein 1A/B light chain3 (LC3) in fibroblasts from 2 affected dogs. The extraneural findings of 9 euthanized LRs and skin biopsies from 4 living affected LRs were examined by light microscopy, electron microscopy, and immunohistochemistry (IHC), using antibodies against autophagosomal membranes (LC3), autophagic cargo (p62), and lysosomal membranes (LAMP2). Biochemical screening of urine and fibroblasts of 2 affected dogs was performed. Under basal conditions, the affected fibroblasts contained significantly more LC3-II and LC3-positive vesicles than did the controls. Morphologically, several cells, including serous secretory epithelium, endothelial cells, pericytes, plasma cells, and macrophages, contained cytoplasmic vacuoles with an ultrastructure resembling enlarged amphisomes, endosomes, or multivesicular bodies. IHC showed strong membranous LAMP2 positivity only in sweat glands. The results show that basal but not induced autophagy is altered in affected fibroblasts. The ultrastructure of affected cells is compatible with altered autophagic and endo-lysosomal vesicular traffic. The findings in this spontaneous disease provide insight into possible tissue-specific roles of basal autophagy.

Re-emergence of hereditary polyneuropathy in Scandinavian Alaskan malamute dogs-old enemy or new entity? A case series.

A homozygous mutation has been identified in the N-myc downstream-regulated gene 1 (NDRG1) in recent cases of polyneuropathy in Alaskan malamute dogs from the Nordic countries and USA. The objective of the present study was to determine if cases diagnosed 30-40 years ago with polyneuropathy in the Alaskan malamute breed in Norway had the same hereditary disease as the recent cases. Fourteen historical cases and 12 recently diagnosed Alaskan malamute dogs with hereditary polyneuropathy, and their parents and littermates (n = 88) were included in this study (total n = 114). After phenotyping of historical and recent cases, NDRG1 genotyping was performed using DNA extracted from archived material from five Norwegian dogs affected by the disease in the late 1970s and 1980s. In addition, pedigrees were analysed. Our study concluded that historical and recent phenotypic polyneuropathy cases were carrying the same NDRG1-mutation. The pedigree analysis showed that all affected Alaskan malamute cases with polyneuropathy could be traced back to one common ancestor of North American origin. By this study, a well-documented example of the silent transmission of recessive disease-causing alleles through many generations is provided, demonstrated by the re-emergence of a phenotypically and genetically uniform entity in the Scandinavian Alaskan malamute population.

Temporary hindlimb paresis following dystocia due to foetal macrosomia in a Celebes crested macaque (Macaca nigra).

A multiparous Celebes crested macaque presented with dystocia due to foetal macrosomia, causing foetal mortality and hindlimb paresis. After emergency caesarean section, recovery of motor function took 1 month before hindlimbs were weight bearing and 2 months before re-integration with the troop.

Clinical characteristics of epilepsy of unknown origin in the Rottweiler breed.

BACKGROUND: Epilepsy is one of the most common neurological conditions in dogs. Despite that epilepsy appears to be common in the Rottweiler breed, published literature about the phenotype of epilepsy in this breed is lacking. The aim of this questionnaire-based study was to describe the clinical characteristics of epilepsy in the Rottweiler breed including; signalment, pedigree, housing conditions and information about the seizures such as age at onset, seizure type, duration, and progression, as well as number of seizure days (24 h), effect and side effects of anti-epileptic drugs, and potential comorbidities. The diagnosis for epilepsy of unknown origin was based on the following inclusion criteria: ≥2 seizure days, starting between 6 months and 7 years of age, no known history of poisoning or serious head trauma, and (when available), pre-study routine serum biochemical parameters were within the reference intervals. RESULTS: A total of 37 cases (23 females and 14 males) were included in the study. The median age at onset of seizures was 36 months (range 8-84 months). The dogs suffered from generalized tonic-clonic seizures, and more than 50 % of the dogs had experienced cluster seizures (>1 seizure in 24 h). The dogs commonly started to seizure while resting (23/36) and/or sleeping (20/36). Only 3 of the 36 dogs experienced seizures during activities such as walking or training. All of the 24/37 (64.9 %) dogs on antiepileptic drugs received phenobarbital. Five dogs needed add-on treatment (n = 5), and of these: one dog was on 3 drugs (phenobarbital, potassium bromid and levetiracetam) (n = 1), three dogs were on phenobarbital and potassium bromide (n = 3), and one dog received phenobarbital and imepitoin (n = 1). Seizure frequency did not necessarily improve following antiepileptic treatment, and for six of 21 (28.6 %) of the dogs, seizure frequency increased. All of the Rottweilers in this study had relatives with epilepsy reported. CONCLUSIONS: The Rottweilers suffering from epilepsy in this study presented with generalized tonic-clonic seizures, and their response to antiepileptic treatment was variable. More than 50 % of the dogs had experienced cluster seizures (>1 seizure in 24 h).

TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.

Clinical, pathological and genetic examination revealed an as yet uncharacterized juvenile-onset neuroaxonal dystrophy (NAD) in Spanish water dogs. Affected dogs presented with various neurological deficits including gait abnormalities and behavioral deficits. Histopathology demonstrated spheroid formation accentuated in the grey matter of the cerebral hemispheres, the cerebellum, the brain stem and in the sensory pathways of the spinal cord. Iron accumulation was absent. Ultrastructurally spheroids contained predominantly closely packed vesicles with a double-layered membrane, which were characterized as autophagosomes using immunohistochemistry. The family history of the four affected dogs suggested an autosomal recessive inheritance. SNP genotyping showed a single genomic region of extended homozygosity of 4.5 Mb in the four cases on CFA 8. Linkage analysis revealed a maximal parametric LOD score of 2.5 at this region. By whole genome re-sequencing of one affected dog, a perfectly associated, single, non-synonymous coding variant in the canine tectonin beta-propeller repeat-containing protein 2 (TECPR2) gene affecting a highly conserved region was detected (c.4009C>T or p.R1337W). This canine NAD form displays etiologic parallels to an inherited TECPR2 associated type of human hereditary spastic paraparesis (HSP). In contrast to the canine NAD, the spinal cord lesions in most types of human HSP involve the sensory and the motor pathways. Furthermore, the canine NAD form reveals similarities to cases of human NAD defined by widespread spheroid formation without iron accumulation in the basal ganglia. Thus TECPR2 should also be considered as candidate gene for human NAD. Immunohistochemistry and the ultrastructural findings further support the assumption, that TECPR2 regulates autophagosome accumulation in the autophagic pathways. Consequently, this report provides the first genetic characterization of juvenile canine NAD, describes the histopathological features associated with the TECPR2 mutation and provides evidence to emphasize the association between failure of autophagy and neurodegeneration.

A KCNJ10 mutation previously identified in the Russell group of terriers also occurs in Smooth-Haired Fox Terriers with hereditary ataxia and in related breeds.

BACKGROUND: Hereditary ataxias with similar phenotypes were reported in the Smooth-Haired Fox Terrier, the Jack Russell Terrier and the Parson Russell Terrier. However, segregation analyses showed differing inheritance modes in these breeds. Recently, molecular genetic studies on the Russell group of terriers found independent mutations in KCNJ10 and CAPN1, each associated with a specific clinical subtype of inherited ataxia. The aim of this study was to clarify whether or not Smooth-Haired Fox Terriers with hereditary ataxia and dogs of other related breeds harbor either of the same mutations. A sub goal was to update the results of KCNJ10 genotyping in Russell group terriers. FINDINGS: Three Smooth-Haired Fox Terriers with hereditary ataxia and two Toy Fox Terriers with a similar phenotype were all homozygous for the KCNJ10 mutation. The same mutation was also found in a heterozygous state in clinically unaffected Tenterfield Terriers (n = 5) and, in agreement with previous studies, in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers. CONCLUSIONS: A KCNJ10 mutation, previously associated with an autosomal recessive spinocerebellar ataxia in Jack Russell Terriers, Parson Russell Terriers, and Russell Terriers segregates in at least three more breeds descended from British hunting terriers. Ataxic members of two of these breeds, the Smooth-Haired Fox Terrier and the Toy Fox Terrier, were homozygous for the mutation, strengthening the likelihood that this genetic defect is indeed the causative mutation for the disease known as "hereditary ataxia" in Fox Terriers and "spinocerebellar ataxia with myokymia, seizures or both" in the Russell group of terriers.

Validation of the diagnosis canine epilepsy in a Swedish animal insurance database against practice records.

Canine epilepsy is one of the most common neurological conditions in dogs but the actual incidence of the disease remains unknown. A Swedish animal insurance database has previously been shown useful for the study of disease occurrence in companion animals. The dogs insured by this company represent a unique population for epidemiological studies, because they are representative of the general dog population in Sweden and are followed throughout their life allowing studies of disease incidence to be performed. The database covers 50% of all insured dogs (in the year 2012) which represents 40% of the national dog population. Most commonly, dogs are covered by both veterinary care insurance and life insurance. Previous studies have shown that the general data quality is good, but the validity of a specific diagnosis should be examined carefully before using the database for incidence calculations. The aim of the current study was therefore to validate the information contained in the insurance database regarding canine epilepsy. The validation focused on the positive predictive value and the data-transfer from the veterinary practice records to the insurance database. The positive predictive value was defined as the proportion of recorded cases that actually had the disease in question. The quality of the data-transfer was assessed by comparing the diagnostic codes in practice records to the codes in the insurance database. The positive predictive value of the diagnostic codes for canine epilepsy (combining "epileptic convulsions" and "idiopathic epilepsy") in the insurance database was validated in a cross-sectional study where insurance claims for canine epilepsy were compared to diagnostic information in practice records. A random sample of dogs with a reimbursed insurance claim during 2006 was included in the study sample (n=235). Practice records were requested by mail from attending veterinarians. Two independent examiners scrutinized all the records. All 235 dogs were coded correctly in the database as they really had suffered seizures with or without convulsions, and the quality of the data-transfer was therefore excellent. In total, 167 dogs (71%) were classified as cases of canine epilepsy according to pre-defined criteria, and the positive predictive value was therefore considered relatively high. Based on these results, it was concluded that the data regarding canine epilepsy in the insurance database can be used for further population studies.

Borna disease virus infection in cats.

Bornaviruses are known to cause neurological disorders in a number of animal species. Avian Bornavirus (ABV) causes proventricular dilatation disease (PDD) in birds and Borna disease virus (BDV) causes Borna disease in horses and sheep. BDV also causes staggering disease in cats, characterised by ataxia, behavioural changes and loss of postural reactions. BDV-infection markers in cats have been reported throughout the world. This review summarizes the current knowledge of Borna disease viruses in cats, including etiological agent, clinical signs, pathogenesis, epidemiology and diagnostics, with comparisons to Bornavirus infections in other species.

Expression of interferon gamma in the brain of cats with natural Borna disease virus infection.

Borna disease virus (BDV) is a neurotropic, negative-stranded RNA virus, which causes a non-suppurative meningoencephalomyelitis in a wide range of animals. In cats, BDV infection leads to staggering disease. In spite of a vigorous immune response the virus persists in the central nervous system (CNS) in both experimentally and naturally infected animals. Since the CNS is vulnerable to cytotoxic effects mediated via NK-cells and cytotoxic T-cells, other non-cytolytic mechanisms such as the interferon (IFN) system is favourable for viral clearance. In this study, IFN-γ expression in the brain of cats with clinical signs of staggering disease (N=12) was compared to the expression in cats with no signs of this disease (N=7) by quantitative RT-PCR. The IFN-γ expression was normalised against the expression of three reference genes (HPRT, RPS7, YWHAZ). Cats with staggering disease had significantly higher expression of IFN-γ compared to the control cats (p-value ≤ 0.001). There was no significant difference of the IFN-γ expression in BDV-positive (N=7) and -negative (N=5) cats having clinical signs of staggering disease. However, as BDV-RNA still could be detected, despite an intense IFN-γ expression, BDV needs to have mechanisms to evade this antiviral immune response of the host, to be able to persist.

A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy.

The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

Acquired motor neuron loss causing severe pelvic limb contractures in a young cat.

PRESENTATION: This report describes a kitten with paraplegia and extensor rigidity of the pelvic limbs associated with motor neuron loss and chronic denervation of skeletal muscle. Persistent skeletal muscle atrophy and degeneration had resulted in immobile stifle and hock joints and severe pelvic limb rigidity consistent with a neurogenic form of arthrogryposis. Both pelvic limbs were equally affected and the kitten showed no signs of pain. INVESTIGATIONS: Electromyography identified spontaneous activity in the pelvic limbs. Muscle and peripheral nerve biopsies showed pathology consistent with denervation. On necropsy, 3 weeks after admittance, severe degenerative changes including axonal necrosis and myelin degeneration were confirmed in the lumbar spinal cord. CLINICAL RELEVANCE: There are very few descriptions of feline motor neuron degeneration in the literature and obtaining an ante-mortem diagnosis is difficult. Although an inherited disorder cannot be ruled out, a condition acquired congenitally in utero or postnatally was suspected in this case.

Sensory ataxic neuropathy in golden retriever dogs is caused by a deletion in the mitochondrial tRNATyr gene.

Sensory ataxic neuropathy (SAN) is a recently identified neurological disorder in golden retrievers. Pedigree analysis revealed that all affected dogs belong to one maternal lineage, and a statistical analysis showed that the disorder has a mitochondrial origin. A one base pair deletion in the mitochondrial tRNA(Tyr) gene was identified at position 5304 in affected dogs after re-sequencing the complete mitochondrial genome of seven individuals. The deletion was not found among dogs representing 18 different breeds or in six wolves, ruling out this as a common polymorphism. The mutation could be traced back to a common ancestor of all affected dogs that lived in the 1970s. We used a quantitative oligonucleotide ligation assay to establish the degree of heteroplasmy in blood and tissue samples from affected dogs and controls. Affected dogs and their first to fourth degree relatives had 0-11% wild-type (wt) sequence, while more distant relatives ranged between 5% and 60% wt sequence and all unrelated golden retrievers had 100% wt sequence. Northern blot analysis showed that tRNA(Tyr) had a 10-fold lower steady-state level in affected dogs compared with controls. Four out of five affected dogs showed decreases in mitochondrial ATP production rates and respiratory chain enzyme activities together with morphological alterations in muscle tissue, resembling the changes reported in human mitochondrial pathology. Altogether, these results provide conclusive evidence that the deletion in the mitochondrial tRNA(Tyr) gene is the causative mutation for SAN.

Cerebral ventricular size in developing normal kittens measured by ultrasonography.

To evaluate the age of fontanelle closure of normal kittens and the size of their lateral ventricles, 50 ultrasonographic examinations using the bregmatic fontanelle as an acoustic window were made. Seven kittens, laboratory animals, were included in the study. To verify the location of the lateral ventricle, two of the kittens were sacrificed as neonates. In one of them ink was injected prior to autopsy into one lateral ventricle under sonographic guidance. In a longitudinal study of five of the kittens, the skull depth and the depth of the central part of the lateral ventricle reproduced in a longitudinal view could be measured up to the age of about 5 months. During that period, the skull depth increased from a median value of 1.95 cm (1.92-1.98) in a seven-day-old cat to 2.58 cm (2.52-2.59) in a 154-day-old cat, while the afore-mentioned ventricle values increased from 0.3 mm to 1.1 mm.