Electroencephalography findings in healthy and Finnish Spitz dogs with epilepsy: visual and background quantitative analysis

BACKGROUND: Qualitative and quantitative electroencephalography (EEG) parameters of healthy and Finnish Spitz dogs with epilepsy have not been determined. OBJECTIVE: To determine if EEG can provide specific characteristics to distinguish between healthy dogs and dogs with epilepsy. ANIMALS: Sixteen healthy and 15 Finnish Spitz dogs with epilepsy. METHODS: A prospective clinical EEG study performed under medetomidine sedation. Blinded visual and quantitative EEG analyses were performed and results were compared between study groups. RESULTS: Benign epileptiform transients of sleep and sleep spindles were a frequent finding in a majority of animals from both groups. The EEG analysis detected epileptiform activity in 3 Finnish Spitz dogs with epilepsy and in 1 healthy Finnish Spitz dog. Epileptiform activity was characterized by spikes, polyspikes, and spike slow wave complexes in posterior-occipital derivation in dogs with epilepsy and with midline spikes in control dog. The healthy dogs showed significantly less theta and beta activity than did the dogs with epilepsy (P < .01), but the only significant difference between healthy dogs and dogs with untreated epilepsy was in the alpha band (P < .001). Phenobarbital treatment increased alpha, beta (P < .001), and theta (P < .01), and decreased delta (P < .001) frequency bands compared with dogs with untreated epilepsy. CONCLUSIONS AND CLINICAL IMPORTANCE: Benign epileptiform transients of sleep could be easily misinterpreted as epileptiform activity. Epileptiform activity in Finnish Spitz dogs with epilepsy seems to originate from a posterior-occipital location. The EEG of dogs with epilepsy exhibited a significant difference in background frequency bands compared with the control dogs. Phenobarbital treatment markedly influenced all background activity bands. Quantitative EEG analysis, in addition to visual analysis, seems to be a useful tool in the examination of patients with epilepsy.     

CEREBRAL GLUCOSE UTILIZATION MEASURED WITH HIGH RESOLUTION POSITRON EMISSION TOMOGRAPHY IN EPILEPTIC FINNISH SPITZ DOGS AND HEALTHY DOGS

In human epileptic patients, changes in cerebral glucose utilization can be detected 2‐deoxy‐2‐[¹⁸F] fluoro‐d ‐glucose positron emission tomography (FDG‐PET). The purpose of this prospective study was to determine whether epileptic dogs might show similar findings. Eleven Finnish Spitz dogs with focal idiopathic epilepsy and six healthy dogs were included. Dogs were examined using electroencephalography (EEG) and FDG‐PET, with epileptic dogs being evaluated during the interictal period. Visual and semi‐quantitative assessment methods of FDG‐PET were compared and contrasted with EEG findings. Three independent observers, unaware of dog clinical status, detected FDG‐PET uptake abnormalities in 9/11 epileptic (82%), and 4/8 healthy dogs (50%). Occipital cortex findings were significantly associated with epileptic status (P = 0.013). Epileptic dogs had significantly lower standardized uptake values (SUVs) in numerous cortical regions, the cerebellum, and the hippocampus compared to the control dogs. The lowest SUVs were found in the occipital lobe. White matter normalized and left‐right asymmetry index values for all pairs of homologous regions did not differ between groups. Visual evaluation of the EEGs was less sensitive (36%) than FDG‐PET. Both diagnostic tests were consensual and specific (100%) for occipital findings, but EEG had a lower sensitivity for detecting lateralized foci than FDG‐PET. Findings supported the use of FDG‐PET as a diagnostic test for dogs with suspected idiopathic epilepsy. Visual and semiquantitative analyses of FDG‐PET scans provided complementary information. Findings also supported the theory that epileptogenesis may occur in multiple brain regions in Finnish Spitz dogs with idiopathic epilepsy.     

Feline hippocampal and piriform lobe necrosis as a consequence of severe cluster seizures in two cats in Finland

Feline hippocampal and piriform lobe necrosis (FHN) has been reported from several countries worldwide and is considered an important aetiology for feline epileptic seizures. The aetiology of FHN remains unclear, however it is suspected that FHN might occur secondary to intense epileptic activity as described in humans and dogs although this has not yet been documented in cats. The purpose of our report is to describe the first cases of FHN in Finland diagnosed by magnetic resonance imaging (MRI) and histopathology. The two cases we describe had a well documented history of pre-existing seizures with normal brain MRI at the onset of cluster seizures but MRI done when the cats exhibited clinical deterioration secondary to severe seizure activity, revealed lesions in the hippocampus and piriform lobes typical of FHN. Our report confirms that feline hippocampus and piriform lobe necrosis does occur in the Finnish cat population and should therefore be considered as a differential diagnosis in cats with seizures. In addition, the presentation, clinical findings, results of MRI and/or histopathology shows that cats may develop FHN secondary to severe seizure activity.     

FDG‐PET IN HEALTHY AND EPILEPTIC LAGOTTO ROMAGNOLO DOGS AND CHANGES IN BRAIN GLUCOSE UPTAKE WITH AGE

Regional cerebral metabolism and blood flow can be measured noninvasively with positron emission tomography (PET). 2‐[¹⁸F]fluoro‐2‐deoxy‐D‐glucose (FDG) widely serves as a PET tracer in human patients with epilepsy to identify the seizure focus. The goal of this prospective study was to determine whether juvenile or adult dogs with focal‐onset epilepsy exhibit abnormal cerebral glucose uptake interictally and whether glucose uptake changes with age. We used FDG‐PET to examine six Lagotto Romagnolo dogs with juvenile epilepsy, two dogs with adult‐onset epilepsy, and five control dogs of the same breed at different ages. Three researchers unaware of dog clinical status visually analyzed co‐registered PET and magnetic resonance imaging (MRI) images. Results of the visual PET analyses were compared with electroencephalography (EEG) results. In semiquantitative analysis, relative standard uptake values (SUV) of regions of interest (ROI) drawn to different brain regions were compared between epileptic and control dogs. Visual analysis revealed areas of hypometabolism interictally in five out of six dogs with juvenile epilepsy in the occipital, temporal, and parietal cortex. Changes in EEG occurred in three of these dogs in the same areas where PET showed cortical hypometabolism. Visual analysis showed no abnormalities in cerebral glucose uptake in dogs with adult‐onset epilepsy. Semiquantitative analysis detected no differences between epileptic and control dogs. This result emphasizes the importance of visual analysis in FDG‐PET studies of epileptic dogs. A change in glucose uptake was also detected with age. Glucose uptake values increased between dog ages of 8 and 28 weeks and then remained constant.     

Brain proton magnetic resonance spectroscopy findings in a Beagle dog with genetically confirmed Lafora disease

Cortical atrophy has been identified using magnetic resonance imaging (MRI) in humans and dogs with Lafora disease (LD). In humans, proton magnetic resonance spectroscopy (1HMRS) of the brain indicates decreased N-acetyl-aspartate (NAA) relative to other brain metabolites. Brain 1HMRS findings in dogs with LD are lacking. A 6-year-old female Beagle was presented with a history of a single generalized tonic-clonic seizure and episodic reflex myoclonus. Clinical, hematological, and neurological examination findings and 3-Tesla MRI of the brain were unremarkable. Brain 1HMRS with voxel positioning in the thalamus was performed in the affected Beagle. It identified decreased amounts of NAA, glutamate-glutamine complex, and increased total choline and phosphoethanolamine relative to water and total creatine compared with the reference range in healthy control Beagles. A subsequent genetic test confirmed LD. Abnormalities in 1HMRS despite lack of changes with conventional MRI were identified in a dog with LD.     

Benign familial juvenile epilepsy in Lagotto Romagnolo dogs

BACKGROUND: Idiopathic childhood epilepsies with benign outcomes are well recognized in human medicine, but are not reported in veterinary literature. We recognized such a neurologic syndrome in Lagotto Romagnolo dogs. ANIMALS: Twenty-five Lagotto Romagnolo puppies from 9 different litters examined because of simple or complex focal seizures and 3 adult Lagotto Romagnolo dogs exhibiting similar clinical signs were used. METHODS: Clinical and diagnostic evaluations of affected dogs were conducted, including electromyography, electroencephalography, and other testing. RESULTS: Seizures in puppies began at 5 to 9 weeks of age and usually resolved spontaneously by 8 to 13 weeks. Those with the most severe seizures also had signs of neurologic disease between these seizures, including generalized ataxia and hypermetria. There were no abnormalities in routine laboratory screenings of blood, urine, and cerebrospinal fluid. Electromyography, brainstem auditory-evoked potentials, and magnetic resonance imaging revealed no specific and consistent abnormalities. Fourteen of 16 (87.5%) affected puppies and 2 of 3 (67%) adult dogs revealed epileptiform activity in the electroencephalogram. Histopathologic examination in 1 puppy and 1 adult dog revealed lesions of Purkinje cell inclusions and vacuolation of their axons restricted to the cerebellum. Pedigree analysis suggests an autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder, with simple or complex focal seizures and cerebellar lesions, represents a newly recognized epileptic syndrome in dogs.     

REVERSIBLE MAGNETIC RESONANCE IMAGING ABNORMALITIES IN DOGS FOLLOWING SEIZURES

Reversible magnetic resonance (MR) imaging lesions have been described in humans following seizures. This condition has not yet been reported in animals. This paper describes reversible abnormalities identified in 3 dogs using MR imaging that was performed initially within 14 days of the last seizure and follow-up imaging that was performed after 10 to 16 weeks of anticonvulsant therapy. All three dogs had lesions in the piriform/temporal lobes, characterized by varying degrees of hyperintensity on T2-weighted images and hypointensity on T1-weighted images. In one dog, contrast enhancement was evident. On reevaluation, partial resolution occurred in all 3 dogs. In a fourth animal with an olfactory meningioma, similar appearing lesions in the temporal cortex and right and left piriform lobes were identified after seizure activity. A surgical biopsy of the temporal cortex and hippocampus was performed and edema, neovascularization, reactive astrocytosis, and acute neuronal necrosis were evident. These histologic findings are similar to those reported in humans with seizures. Recognizing the potential occurrence of reversible abnormalities in MR images is important in developing a diagnostic and therapeutic plan in canine patients with seizures. Repeat imaging after seizure control may help differentiate between seizure-induced changes and primary multifocal parenchymal abnormalities.     

Electroencephalographic evaluation of gold wire implants inserted in acupuncture points in dogs with epileptic seizures

The purpose of this study was to evaluate both, clinically and with electroencephalographic (EEG) recordings, the effect of gold wire implants in acupuncture points in dogs with uncontrolled idiopathic epileptic seizures. Fifteen dogs with such diagnosis were enrolled in the study. A first EEG recording was performed in all dogs under anaesthesia with xylazine (1 mg/kg) and propofol (6 mg/kg) before the treatment protocol, and a second EEG was performed 15 weeks later. Relative frequency power, intrahemispheric coherence available through EEG, number of seizures and seizure severity were compared before and after treatment using a Wilcoxon signed-rank test. There were no significant statistical differences before and after treatment in relative power or in intrahemispheric coherence in the EEG recording. However, there was a significant mean difference in seizure frequency and seizure severity between control and treatment periods. After treatment, nine of the 15 dogs (60%) had at least a 50% reduction in seizures frequency during the 15 weeks established as follow-up of this treatment.     

Results of cerebrospinal fluid analysis, neurologic examination findings, and age at the onset of seizures as predictors for results of magnetic resonance imaging of the brain in dogs examined because of seizures: 115 cases (1992-2000)

OBJECTIVE: To determine whether neurologic examination findings, results of CSF analysis, or age at the onset of seizures could be used to predict whether results of magnetic resonance imaging (MRI) would be normal or abnormal in dogs with seizures. DESIGN: Retrospective study. ANIMALS: 115 dogs. PROCEDURE: Information on results of neurologic examination, results of CSF analysis, age at the onset of seizures, and results of MRI was obtained from the medical records. RESULTS: Results of MRI were abnormal in 61 dogs and normal in 54. Sensitivity and specificity of neurologic examination alone were 77 (47/61) and 91% (49/54), respectively. Sensitivity and specificity of CSF analysis alone were 79 (48/61) and 69% (37/54), respectively. Results of MRI were abnormal for 12 of 28 (43%) dogs with abnormal CSF analysis results and normal neurologic examination results but for only 2 of 35 (6%) dogs with normal CSF analysis and normal neurologic examination results. Similarly, results of MRI were abnormal for 36 of 37 (97%) dogs with abnormal CSF analysis and abnormal neurologic examination results but for only 11 of 15 (73%) dogs with normal CSF analysis results and abnormal neurologic examination results. Age at the onset of seizures (< 6 vs > or = 6 years old) was not significantly associated with results of MRI. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that neurologic examination findings and results of CSF analysis are useful in predicting whether results of MRI will be abnormal in dogs examined because of seizures, but age at the onset of seizures is not.     

Canine intracranial neoplasia: clinical risk factors for development of epileptic seizures

Objectives : To identify clinical risk factors for seizures in dogs with intracranial neoplasia. Methods : A cross‐sectional retrospective study of 68 dogs with histopathologically confirmed primary or secondary intracranial neoplasia, complete clinical history and magnetic resonance imaging of the brain was conducted. Signalment and clinical history were retrieved from clinical records and magnetic resonance images of the brain were re‐evaluated. Prevalence of findings was compared between dogs with and without seizures. Results : Forty‐two dogs had tumour‐related seizures, the remaining 26 were seizure‐free. Tumour types included meningioma (23 dogs with and 5 without seizures), glioma (9 dogs with and 6 without seizures), choroid plexus tumour (2 dogs without seizures), neuroblastoma (1 dog with seizures) and metastatic/invasive tumours including lymphoma (9 dogs with and 13 without seizures). On the basis of multi‐variable logistic regression analysis, risk factors for seizures associated with intracranial neoplasia were magnetic resonance imaging findings consistent with the presence of neoplastic tissue in frontal lobe [odds ratio (OR) 9·61; 95% confidence interval (CI) 2·59 to 35·61], marked gadolinium enhancement (OR 10·41; 95% CI 2·07 to 52·30) and magnetic resonance imaging findings of subfalcine and/or subtentorial herniation (OR 3·88; 95% CI 1·10 to 13·71). Clinical Significance : Dogs with primary or secondary intracranial neoplasia are at risk of seizures, particularly those with tumours that affect the frontal lobe, enhance markedly with gadolinium, or cause subfalcine and/or subtentorial herniation.     

Epilepsy and seizure classification in 63 dogs: a reappraisal of veterinary epilepsy terminology

The human definitions of epilepsy and seizure classification were applied rigidly to epileptic dogs to investigate whether the distribution of the seizure types and epilepsies of dogs is comparable to that of human beings. Sixty-three dogs were referred because of recurrent (> 2) epileptic seizures. Only dogs without previous or ongoing antiepileptic treatment were included. All dogs had a physical and neurologic examination and blood work that included a CBC and a biochemical profile. All owners were asked to complete a questionnaire, focusing on seizure development. In addition, video recordings of suspected seizure episodes were analyzed if available. In the majority of dogs where an intracranial lesion was suspected, a computerized tomography scan was performed. Sixty-five percent of the dogs experienced partial seizures with or without secondary generalization and 32% exhibited primary generalized seizures; in 3% of the dogs the seizures could not be classified. Twenty-five percent of these cases were classified as idiopathic, 16% as symptomatic, and 45% as cryptogenic epilepsy; in 14% of these a classification was not possible. Applying human definitions, the distribution of seizure types and epilepsy classifications in these dogs differed widely from those in previous reports of canine epilepsy, where generalized seizures and idiopathic epilepsy were most frequently reported. However, our findings are consistent with the results of several large studies of human epilepsy patients. In dogs with epilepsy, closer attention must be given to the detection of a partial onset of seizures. In this study, detailed questioning of the owners and when possible analysis of video recorded seizures, proved to be sufficient for diagnosing seizures with a partial onset in a significant number of dogs. Partial onset of seizures may be an indication of underlying cerebral pathology. Some adjustments of veterinary epilepsy terminology are suggested.     

Feline Temporal Lobe Epilepsy: Review of the Experimental Literature

Accumulating evidence suggests that epileptic seizures originating from the temporal lobe (TL) occur in cats. Typically, affected animals have clinically focal seizures with orofacial automatisms including salivation, facial twitching, lip smacking, chewing, licking, and swallowing. Motor arrest and autonomic and behavioral signs also may occur. Many affected cats have magnetic resonance imaging (MRI) changes within the hippocampus or histopathologically confirmed hippocampal sclerosis or necrosis. From the 1950s to the 1980s, cats frequently were used as animal models for neurophysiological experiments and electrophysiological studies, from which important basic knowledge about epilepsy originated, but which has been rarely cited in clinical veterinary studies. These studies were reviewed. Experimental research on cats showed the widespread anatomical connections among TL structures. The ictal clinical signs originating from the hippocampus, amygdala, or lateral temporal cortex are similar, because of their dense interconnections. The ictal signs can be divided into autonomic, somatic, and behavioral. For research purposes, a 6‐stage system was established, reflecting the usual sequential progression from focal to generalized seizure: attention response (1), arrest (2), salivation, licking (3), facial twitching (4), head turning or nodding (5), and generalized clonic convulsions (6). Knowledge of this data may help in recognizing low‐stage (stage 1 or stage 2) epileptic seizures in clinical practice. Early experimental research data are in accordance with recent clinical observations regarding ictal clinical signs of TL epileptic seizures in cats. Furthermore, the research data supports the idea that TL epilepsy represents a unique clinical entity with a specific seizure type and origin in cats.     

One-year clinical and magnetic resonance imaging follow-up of Doberman Pinschers with cervical spondylomyelopathy treated medically or surgically

OBJECTIVE: To evaluate progression of clinical signs and magnetic resonance imaging (MRI) findings in dogs with cervical spondylomyelopathy (wobbler syndrome) treated medically or surgically. DESIGN: Prospective cohort study. ANIMALS: 12 Doberman Pinschers. PROCEDURES: Neurologic examinations and MRI were performed before medical (n = 9) or surgical treatment (ventral slot, 3) and a minimum of 12 months later. RESULTS: Mean follow-up time was 14.5 months. Clinically, 2 dogs improved after surgical treatment and 5 improved after medical treatment. Magnetic resonance imaging of surgically treated dogs revealed adequate spinal cord decompression. Spinal cord signal changes were seen in 2 dogs before surgery, both of which had new signal changes at the same and adjacent sites during follow-up examination. One dog treated surgically developed 3 new areas of spinal cord compression. In the medically treated dogs, the severity of spinal cord compression at the time of follow-up examination was unchanged in 4 dogs, worse in 2 dogs, and improved in 3 dogs, but spinal cord atrophy was observed on transverse images. Four medically treated dogs had changes in spinal cord signal initially, but none developed new signal changes or compressions. CONCLUSIONS AND CLINICAL RELEVANCE: Medical and surgical treatment improved or stabilized the clinical condition of most dogs. Surgical treatment appeared to hasten the development of additional areas of spinal cord compression and lesions in dogs with preoperative cord changes; however, the clinical importance of these changes was not determined. The progression of pathologic MRI abnormalities was notably less in medically treated dogs, compared with surgically treated dogs.     

Magnetic resonance imaging in two dogs with central nervous system disease

Accurate localization of the lesions in two dogs with progressive neurological disease was demonstrated with magnetic resonance imaging (MRI). The first dog had unilateral cerebellar signs with associated paradoxical vestibular symptoms. The CSF tap and clinical localization suggested a right-sided cerebellar tumour and this was confirmed with MRI scanning. The second dog had predominantly asymmetrical fore-brain signs with circling, personality changes, seizures and contralateral proprioceptive deficits. CSF analysis suggested an inflammatory or neoplastic condition. MRI showed a diffuse oedematous lesion of the left cerebral hemisphere which corresponded exactly with the lesions seen at necropsy. The advantages of MRI over CT scans are discussed.     

A retrospective study on the use of acepromazine maleate in dogs with seizures

Use of acepromazine (i.e., acetylpromazine) maleate in dogs with a history of seizures is reportedly contraindicated because of the risk of decreasing the seizure threshold in these animals. In this retrospective study, acepromazine was administered for tranquilization to 36 dogs with a prior history of seizures and to decrease seizure activity in 11 dogs. No seizures were seen within 16 hours of acepromazine administration in the 36 dogs that received the drug for tranquilization during hospitalization. After acepromazine administration, seizures abated for 1.5 to 8 hours (n=6) or did not recur (n=2) in eight of 10 dogs that were actively seizing. Excitement-induced seizure frequency was reduced for 2 months in one dog.     

Subdural hematoma of the brainstem in a dog: magnetic resonance findings and treatment

An 8-year-old, spayed female Dalmatian with a history of seizures was evaluated for cervical pain and bilateral scleral hemorrhages. Diagnostic evaluations revealed a mass displacing the ventral brainstem on magnetic resonance imaging (MRI). The mass was surgically removed and histologically confirmed to be a hematoma. The dog's neurological signs resolved completely after surgery. Although extradural, subdural, subarachnoid, and intraparenchymal hemorrhages have been reported in dogs and cats, this is the first known report of a subdural hematoma of the ventral brainstem in a dog. On the basis of the history and the appearance of the subdural hematoma on MRI, a traumatic event during the seizure episodes was considered the most likely cause of the subdural hematoma in this case.     

Interictal electroencephalographic findings in a family of golden retrievers with idiopathic epilepsy

This study investigated how far electro-encephalographic (EEG) testing may help in the confirmation of idiopathic epilepsy (IE) in dogs. We found significantly constant (P < 0.05) and similar values of amplitude and frequency under medetomidine/propofol anaesthesia. The baseline pattern of healthy and the background activity of the epileptic dogs were characterised by an homogeneous high voltage slow activity and low voltage fast activity pattern with no significantly different values between tracings. However, we frequently found spindles in all recordings of the epileptic dogs. They impressed by asymmetries as well as significant variation in amplitude and duration. We concluded from these observations that, despite deep anaesthesia, the EEG abnormalities were consistent and extremely important for the confirmation of IE in the dog. In addition, 10 per cent of the offspring in our golden retriever family were positive for spindles, if the EEG was taken at the age of maximal expression. We concluded that this does not mean that this factor is genetically dependent, but that its interaction may increase the liability to contract seizures in the golden retriever. We believe that EEG combined with pedigree analysis may be very helpful in risk assessment of IE in the dog.     

Clinical and genetic investigations of idiopathic epilepsy in the Bernese mountain dog

A study was conducted to investigate the clinical aspects and to define the mode of inheritance of idiopathic epilepsy in the Bernese mountain dog. Pedigree analyses were carried out on an open, non-preselected population of 4005 dogs. Five different subpopulations with 50 epileptic dogs from 13 generations were included. Almost all epileptic patients showed generalised seizures of the grand-mal type with a well-defined prodromal and postictal phase. The majority (62 per cent) of the epileptic dogs had had their first seizures at between one and three years of age and it was found that the age at first seizure was significantly (P < 0.05) lower in dogs from affected parental animals than in dogs from healthy parental animals. A clear predisposition for males was also noted. Additionally, there was no correlation between inbreeding coefficient and age at first seizure or incidence rate of seizures. The increased occurrence of the disease in different subpopulations and different families of the same sires or dams showed that there was a genetic basis for the condition in the Bernese mountain dog. Furthermore, the results of the pedigree analyses and binomial test support the hypothesis that idiopathic epilepsy has a polygenic, recessive mode of inheritance in the breed. Additional objective test-mating programmes would however be necessary to define the exact mode of inheritance.     

A comparison of clinical,magnetic resonance imaging and pathological findings in dogs with gliomatosis cerebri,focusing on cases with minimal magnetic resonance imaging changes‡

The primary study objective was to determine whether clinical examination and magnetic resonance imaging (MRI) can underestimate canine gliomatosis cerebri (GC); we also investigated immunohistochemical features. Seven dogs with GC were studied; four recruited specifically because of minimal MRI changes. Neuroanatomic localization and the distribution of MRI, gross and sub‐gross lesions were compared with the actual histological distribution of neoplastic cells. In six cases, clinical examination predicted focal disease and MRI demonstrated a single lesion or appeared normal. Neoplastic cells infiltrated many regions deemed normal by clinical examination and MRI, and were Olig2‐positive and glial fibrillary acid protein‐negative. Four dogs had concurrent gliomas. GC is a differential diagnosis for dogs with focal neurological deficits and a normal MRI or a focal MRI lesion. Canine GC is probably mainly oligodendrocytic. Type II GC, a solid glioma accompanying diffuse central nervous system neoplastic infiltration, occurs in dogs as in people.