Magnetic resonance imaging features of intracranial granular cell tumors in six dogs.

Magnetic resonance (MR) imaging characteristics of intracranial granular cell tumors (GCTs) have been previously reported in three dogs. The goal of this retrospective study was to examine a larger number of dogs and determine whether distinctive MR characteristics of intracranial GCTs could be identified. Six dogs with histologically confirmed intracranial GCTs and MR imaging were included. Tumor location, size, mass effect, T1- and T2-weighted signal intensity, and peritumoral edema MR characteristics were recorded. In all dogs, GCTs appeared as well-defined, extra-axial masses with a plaque-form, sessile distribution involving the meninges. All tumors were located along the convexity of the cerebrum, the falx cerebri, or the ventral floor of the cranial vault. All tumors were mildly hyperintense on T1-weighted images, and iso- to hyperintense on T2-weighted images. A moderate-to-severe degree of peritumoral edema and mass effect were evident in all dogs. Findings indicated that, while several MR imaging characteristics were consistently identified in canine cerebral GCTs, none of these characteristics were unique or distinctive for this tumor type alone.

Effects of isoflurane anesthesia on cerebrovascular autoregulation in horses.

OBJECTIVE: To test a hypothesis predicting that isoflurane would interfere with cerebrovascular autoregulation in horses and to evaluate whether increased mean arterial blood pressure (MAP) would increase cerebral blood flow and intracranial pressure (ICP) during isoflurane anesthesia. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were anesthetized with isoflurane at a constant end-tidal concentration sufficient to maintain MAP at 60 mm Hg. The facial, carotid, and dorsal metatarsal arteries were catheterized for blood sample collection and pressure measurements. A sub-arachnoid transducer was used to measure ICP Fluorescent microspheres were injected through a left ventricular catheter during MAP conditions of 60 mm Hg, and blood samples were collected. This process was repeated with different-colored microspheres at the same isoflurane concentration during MAP conditions of 80 and 100 mm Hg achieved with IV administration of dobutamine. Central nervous system tissue samples were obtained after euthanasia to quantify fluorescence and calculate blood flow. RESULTS: Increased MAP did not increase ICP or blood flow in any of the brain tissues examined. However, values for blood flow were low for all tested brain regions except the pons and cerebellum. Spinal cord blood flow was significantly decreased at the highest MAP. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that healthy horses autoregulate blood flow in the CNS at moderate to deep planes of isoflurane anesthesia. Nonetheless, relatively low blood flows in the brain and spinal cord of anesthetized horses may increase risks for hypoperfusion and neurologic injury.

Spontaneous canine gliomas: overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping.

Fifty-seven spontaneous canine gliomas were histologically classified and graded using the latest World Health Organization (WHO 2007) criteria for classification of human gliomas. A total of 19 canine astrocytomas were classified as follows: grade IV (GBM) n = 7; grade III n = 5; and grade II, n = 7. Thirty-eight oligodendrogliomas were classified as either grade III (anaplastic) n = 35 or low grade II n = 3. Tissue microarray (TMA) immunohistochemistry was used to evaluate tumor expression of EGFR, PDGFRa and IGFBP2, three key molecules of known pathophysiological importance in human gliomas. Findings were correlated with tumor classification and grade. Increased EGFR expression was demonstrated in 57% of GBMs, 40% of grade III and 28% of grade II astrocytomas. EGFR expression occurred in only 3% of grade III oligodendrogliomas. Increased expression of PDGFRalpha was demonstrated in 43% of GBMs, 20% of grade III, and 14% of grade II astrocytomas. In the oligodendroglioma series, 94% of grade III tumors overexpressed PDGFRalpha. IGFBP2 expression was detected in 71, 60 and 28% of GBMs, grade III and grade II astrocytomas respectively. IGFBP2 expression occurred in 48% of anaplastic and in 33% of low grade oligodendrogliomas. Expression of EGFR, PDGFRalpha or IGFBP2 was not detected in normal canine CNS control TMA cores. The incidence of overexpression of EGFR, PDGFRalpha and IGFBP2 in these canine gliomas closely parallels that in human tumors of similar type and grade. These findings support a role for the spontaneous canine glioma model in directed pathway-targeting therapeutic studies.

Vacuolar myopathy in a dog resembling human sporadic inclusion body myositis.

Sporadic inclusion body myositis (sIBM) is the most common myopathy in people over the age of 50 years. While immune-mediated inflammatory myopathies are well documented in dogs, sIBM has not been described. An 11-year-old dog with chronic and progressive neuromuscular dysfunction was evaluated for evidence of sIBM using current pathologic, immunohistochemical and electron microscopic diagnostic criteria. Vacuoles and congophilic intracellular inclusions were identified in cryostat sections of multiple muscle biopsies and immunostained with antibodies against amyloid-beta peptide, amyloid-beta precursor protein, and proteosome 20S of the ubiquitin-proteosome system. Cellular infiltration and increased expression of MHC Class I antigen were observed. Cytoplasmic filamentous inclusions, membranous structures, and myeloid bodies were identified ultrastructurally. These observations constitute the first evidence that both the inflammatory and degenerative features of human sIBM can occur in a non-human species.

Evaluation of deafness in American Paint Horses by phenotype, brainstem auditory-evoked responses, and endothelin receptor B genotype.

OBJECTIVE: To evaluate deafness in American Paint Horses by phenotype, clinical findings, brainstem auditory-evoked responses (BAERs), and endothelin B receptor (EDNBR) genotype. DESIGN: Case series and case-control studies. ANIMALS: 14 deaf American Paint Horses, 20 suspected-deaf American Paint Horses, and 13 nondeaf American Paint Horses and Pintos. PROCEDURES: Horses were categorized on the basis of coat color pattern and eye color. Testing for the EDNBR gene mutation (associated with overo lethal white foal syndrome) and BAERs was performed. Additional clinical findings were obtained from medical records. RESULTS: All 14 deaf horses had loss of all BAER waveforms consistent with complete deafness. Most horses had the splashed white or splashed white-frame blend coat pattern. Other patterns included frame overo and tovero. All of the deaf horses had extensive head and limb white markings, although the amount of white on the neck and trunk varied widely. All horses had at least 1 partially heterochromic iris, and most had 2 blue eyes. Ninety-one percent (31/34) of deaf and suspected-deaf horses had the EDNBR gene mutation. Deaf and suspected-deaf horses were used successfully for various performance events. All nondeaf horses had unremarkable BAER results. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians should be aware of deafness among American Paint Horses, particularly those with a splashed white or frame overo coat color pattern, blend of these patterns, or tovero pattern. Horses with extensive head and limb markings and those with blue eyes appeared to be at particular risk.

Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

BACKGROUND: Monitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs. HYPOTHESIS/OBJECTIVE: Assessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location. Intraparenchymal transducer placement is associated with more adverse effects. ANIMALS: Seven adult, bred-for-research dogs. METHODS: In a prospective investigational study, microsensor ICP transducers were inserted into subdural and intraparenchymal locations at defined rostral or caudal locations within the rostrotentorial compartment under general anesthesia. Mean arterial pressure and ICP were measured continuously during physiological maneuvers, and for 20 hours after anesthesia. RESULTS: Baseline mean ± SD values for ICP and cerebral perfusion pressure were 7.2 ± 2.3 and 78.9 ± 7.6 mm Hg, respectively. Catheter position did not have a significant effect on ICP measurements. There was significant variation from baseline ICP accompanying physiological maneuvers (P < .001) and with normal activities, especially with changes in head position (P < .001). Pathological sequelae were more evident after intraparenchymal versus subdural placement. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of a microsensor ICP transducer was technically straightforward and provided ICP measurements within previously reported reference ranges. Results support the use of an accessible dorsal location and subdural positioning. Transient fluctuations in ICP are normal events in conscious dogs and large variations associated with head position should be accounted for when evaluating animals with intracranial hypertension.

Muscular dystrophy associated with alpha-dystroglycan deficiency in Sphynx and Devon Rex cats.

Recent studies have identified a number of forms of muscular dystrophy, termed dystroglycanopathies, which are associated with loss of natively glycosylated alpha-dystroglycan. Here we identify a new animal model for this class of disorders in Sphynx and Devon Rex cats. Affected cats displayed a slowly progressive myopathy with clinical and histologic hallmarks of muscular dystrophy including skeletal muscle weakness with no involvement of peripheral nerves or CNS. Skeletal muscles had myopathic features and reduced expression of alpha-dystroglycan, while beta-dystroglycan, sarcoglycans, and dystrophin were expressed at normal levels. In the Sphynx cat, analysis of laminin and lectin binding capacity demonstrated no loss in overall glycosylation or ligand binding for the alpha-dystroglycan protein, only a loss of protein expression. A reduction in laminin-alpha2 expression in the basal lamina surrounding skeletal myofibers was also observed. Sequence analysis of translated regions of the feline dystroglycan gene (DAG1) in affected cats did not identify a causative mutation, and levels of DAG1 mRNA determined by real-time QRT-PCR did not differ significantly from normal controls. Reduction in the levels of glycosylated alpha-dystroglycan by immunoblot was also identified in an affected Devon Rex cat. These data suggest that muscular dystrophy in Sphynx and Devon Rex cats results from a deficiency in alpha-dystroglycan protein expression, and as such may represent a new type of dystroglycanopathy where expression, but not glycosylation, is affected.

Canine model of convection-enhanced delivery of liposomes containing CPT-11 monitored with real-time magnetic resonance imaging: laboratory investigation.

OBJECT: Many factors relating to the safety and efficacy of convection-enhanced delivery (CED) into intracranial tumors are poorly understood. To investigate these factors further and establish a more clinically relevant large animal model, with the potential to investigate CED in large, spontaneous tumors, the authors developed a magnetic resonance (MR) imaging-compatible system for CED of liposomal nanoparticles into the canine brain, incorporating real-time MR imaging. Additionally any possible toxicity of liposomes containing Gd and the chemotherapeutic agent irinotecan (CPT-11) was assessed following direct intraparenchymal delivery. METHODS: Four healthy laboratory dogs were infused with liposomes containing Gd, rhodamine, or CPT-11. Convection-enhanced delivery was monitored in real time by sequential MR imaging, and the volumes of distribution were calculated from MR images and histological sections. Assessment of any toxicity was based on clinical and histopathological evaluation. Convection-enhanced delivery resulted in robust volumes of distribution in both gray and white matter, and real-time MR imaging allowed accurate calculation of volumes and pathways of distribution. RESULTS: Infusion variability was greatest in the gray matter, and was associated with leakage into ventricular or subarachnoid spaces. Complications were minimal and included mild transient proprioceptive deficits, focal hemorrhage in 1 dog, and focal, mild perivascular, nonsuppurative encephalitis in 1 dog. CONCLUSIONS: Convection-enhanced delivery of liposomal Gd/CPT-11 is associated with minimal adverse effects in a large animal model, and further assessment for use in clinical patients is warranted. Future studies investigating real-time monitored CED in spontaneous gliomas in canines are feasible and will provide a unique, clinically relevant large animal translational model for testing this and other therapeutic strategies.

Effects of head-down positioning on regional central nervous system perfusion in isoflurane-anesthetized horses.

OBJECTIVE: To test the hypothesis that head-down positioning in anesthetized horses increases intracranial pressure (ICP) and decreases cerebral and spinal cord blood flows. ANIMALS: 6 adult horses. PROCEDURES: For each horse, anesthesia was induced with ketamine hydrochloride and xylazine hydrochloride and maintained with 1.57% isoflurane in oxygen. Once in right lateral recumbency, horses were ventilated to maintain normocapnia. An ICP transducer was placed in the subarachnoid space, and catheters were placed in the left cardiac ventricle and in multiple vessels. Blood flow measurements were made by use of a fluorescent microsphere technique while each horse was in horizontal and head-down positions. Inferential statistical analyses were performed via repeated-measures ANOVA and Dunn-Sidak comparisons. RESULTS: Because 1 horse developed extreme hypotension, data from 5 horses were analyzed. During head-down positioning, mean +/- SEM ICP increased to 55+/-2 mm Hg, compared with 31+/-2 mm Hg during horizontal positioning; cerebral perfusion pressure was unchanged. Compared with findings during horizontal positioning, blood flow to the cerebrum, cerebellum, and cranial portion of the brainstem decreased significantly by approximately 20% during head-down positioning; blood flows within the pons and medulla were mildly but not significantly decreased. Spinal cord blood flow was low (9 mL/min/100 g of tissue) and unaffected by position. CONCLUSIONS AND CLINICAL RELEVANCE: Head-down positioning increased heart-brain hydrostatic gradients in isoflurane-anesthetized horses, thereby decreasing cerebral blood flow and, to a greater extent, increasing ICP. During anesthesia, CNS regions with low blood flows in horses may be predisposed to ischemic injury induced by high ICP.

Functional neuroanatomy of the domestic rabbit (Oryctolagus cuniculus).

This article reviews clinically relevant neuroanatomy of the central nervous system of the domestic rabbit (Oryctolagus cuniculus) that will help guide veterinarians in localizing neurological disease in this species. Although the vertebral column, spinal cord and brain of rabbits are similar to those of other mammals, features unique to the rabbit are emphasized where they exist.

The neurological examination and lesion localization in the companion rabbit (Oryctolagus cuniculus).

Completion of a thorough neurological examination of a rabbit is essential for clinicians to determine the location of a neurological problem. Determination of the location of a lesion (whether solitary or multifocal/diffuse) enables a clinician to list the most likely causes of the problem. This article presents the neurological examination of the rabbit, followed by a practical guide to lesion localization in this species.

Enhanced gene transfer efficiency in the murine striatum and an orthotopic glioblastoma tumor model, using AAV-7- and AAV-8-pseudotyped vectors.

In this study, recombinant AAV vectors pseudotyped with viral capsids derived from AAV serotypes 7 and 8 were evaluated for gene transfer in the murine striatum relative to vectors pseudotyped with AAV serotypes 2, 5, and 6. In comparison with rAAV serotype 2, pseudotyped vectors derived from AAV-7 and AAV-8 have increased transduction efficiency in the murine CNS, with the rank order rAAV-7 > rAAV-8 > rAAV-5 > rAAV-2 = rAAV-6, with all vectors demonstrating a marked tropism for neuronal transduction. Pseudotyped rAAV vector gene transfer in the brain after preimplantation of a murine 4C8 glioblastoma tumor was also evaluated. Efficiency of gene transfer to the orthotopic tumor was increased when using AAV-6, -7, and -8 capsid proteins in comparison with serotype 2, with the order rAAV-8 = rAAV-7 > rAAV-6 > rAAV-2 > rAAV-5. The increased gene transfer efficiency of rAAV vectors pseudotyped with the rAAV-8 capsid also provided enhanced therapeutic efficacy in a mouse model of glioblastoma multiforme, using vectors encoding an inhibitor of the vascular endothelial growth factor pathway. These studies demonstrate that rAAV vectors pseudotyped with capsids derived from AAV serotypes 7 and 8 provide enhanced gene transfer in the murine CNS and may offer increased therapeutic efficacy in the treatment of neurological disease.

Congenital myopathy with abundant nemaline rods in a cat.

Nemaline myopathy is associated with rod-shaped structures in muscle fibers. At least seven distinct clinical forms have been described in humans and mutations have been identified in five different thin-filament genes. Only a few cases of spontaneously occurring nemaline myopathy have been reported in animals and include an adult-onset form in a family of cats and an early-onset form in a dog. Here, we describe a 2-year-old male, neutered, domestic shorthaired cat that was referred to the Veterinary Medical Teaching Hospital, University of California-Davis, for evaluation of chronic, progressive weakness, and fine tremors. Neurologic deficits were restricted to the neuromuscular system. Electromyography showed mild to moderate diffuse spontaneous activity. Although rod bodies were prominent on light and electron microscopic evaluation of biopsies from several muscles, sarcoplasmic accumulations of dystrophin, desmin, and spectrin also were identified by immunohistochemistry. These findings may represent the occurrence of rod bodies in conjunction with a protein-aggregate myopathy.

Clinical signs, magnetic resonance imaging features, and outcome after surgical and medical treatment of otogenic intracranial infection in 11 cats and 4 dogs.

Brainstem dysfunction resulting from central extension of infection is a life-threatening complication of otitis media/interna (OMI) that has been described infrequently in dogs and cats. We review the clinical signs of disease, diagnostic findings, and results of surgical and medical treatments of brainstem disease attributable to otogenic intracranial infection in cats and dogs. Eleven cats and 4 dogs were examined because of acute, subacute, or chronic clinical signs of brain disease including central vestibular signs, altered mentation, abnormal posture/gait, cranial nerve deficits, and seizures. Results of a minimal database (CBC, serum biochemical panel, urinalysis, thoracic radiographs, and abdominal ultrasonographic images or radiographs) were within reference intervals in all animals. Magnetic resonance (MR) images of the head were acquired for all animals, and cisternal cerebrospinal fluid (CSF) from 9 of 11 cats and 3 of 4 dogs was examined. Surgical exploration and ventral bulla osteotomy were done for 12 of 15 animals, followed by 1-3 months of antibiotic therapy; the remaining animals were euthanized before treatment. In all animals, MR imaging was effective in characterizing the location and extent of the pathologic changes intracranially as well as within middle/inner ear structures. Results of CSF analysis were characteristic of bacterial infection in most of the animals with acute or subacute disease. Since long-term outcome in all treated animals was very good to excellent, it was concluded that dogs and cats with intracranial disease secondary to extension of otitis media/interna have a good-to-excellent prognosis when the condition was diagnosed and was treated by surgical exploration and appropriate antibiotic therapy.

Juvenile idiopathic epilepsy in Egyptian Arabian foals: 22 cases (1985-2005).

BACKGROUND: Epilepsy is relatively uncommon in horses compared with other species and limited information is available. HYPOTHESIS: The objectives of the study were to describe the age of onset, clinical signs, clinicopathologic data, electroeticephalographic findings, treatment, and outcome, including long-term prognosis in Arabian foals with idiopathic epilepsy. ANIMALS: Twenty-two foals were included in the study. MATERIALS AND METHODS: Medical records from 1985 to 2005 were reviewed. RESULTS: The age of onset of affected foals ranged from 2 days to 6 months. Seizures were characterized by generalized tonic and clonic motor activity, staring, and loss of consciousness. The most common postictal signs were transient blindness and abnormal mental status. The interictal neurologic examination was otherwise normal. Clinicopathologic data and imaging diagnostics were normal except in 4 foals that developed complications. Electroencephalography revealed epileptiform activity in 9 of 13 foals. Foals were treated with benzodiazepines for the short-term; whereas phenobarbital was used over the long-term. Potassium bromide was added in 3 foals in which seizures were multiple, frequent, and difficult to control. The long-term prognosis was favorable with cessation of seizures by 1 year of age. The most common complication was head trauma. The most common concurrent disease was pneumonia. CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile idiopathic epilepsy of Egyptian Arabian foals has an early clinical onset but appears to be self-limiting. Information obtained from this study strongly suggests a heritable condition that merits further investigation.

Characteristics of cisternal cerebrospinal fluid associated with intracranial meningiomas in dogs: 56 cases (1985-2004).

OBJECTIVE: To determine CSF characteristics associated with intracranial meningiomas in dogs. DESIGN: Retrospective case series. ANIMALS: 56 dogs with intracranial meningiomas. PROCEDURES: Medical records of dogs with a histopathologic diagnosis of intracranial meningioma, in which CSF analysis had been performed, were reviewed. Information concerning total nucleated cell counts (TNCCs) and differential nucleated cell counts, RBC counts, and total protein concentration in CSF; seizure history and glucocorticoid administration; and location of meningiomas was recorded. RESULTS: TNCCs < 5 cells/microL were detected in 41 of 56 (73%) dogs; 5 of 56 (9%) dogs had TNCCs > 50 cells/microL. Analysis of CSF revealed predominantly neutrophilic pleocytosis in < 20% of dogs. There was a significant association between meningioma location (caudal portion of the cranial fossa or middle and rostral portion of the cranial fossae) and increased TNCCs (> or = 5 cells/microL). CONCLUSIONS AND CLINICAL RELEVANCE: Results were significantly different from those routinely reported in the veterinary literature. Neutrophilic pleocytosis, especially with TNCCs > 50 cells/microL, was not typical in CSF samples from dogs with intracranial meningiomas. Neutrophilic pleocytosis may not be detected in CSF samples from dogs with meningiomas located within the middle or rostral portion of the cranial fossae.

Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans.

Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high-grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy.

Congenital myasthenia gravis in Smooth-Haired Miniature Dachshund dogs.

Three 8-week-old Miniature Smooth Haired Dachshund littermates were diagnosed with myasthenia gravis based on clinical signs, results of electrophysiological testing, and response to the short-acting anticholinesterase drug, edrophonium chloride. Congenital myasthenia gravis was confirmed by the demonstration of decreased acetylcholine-receptor density in external intercostal muscle in the absence of demonstrable serum antiacetylcholine receptor antibody or antibodies complexed to acetylcholine receptors in muscle biopsy samples. Unlike most previously reported cases of congenital myasthenia gravis that are relentlessly progressive, clinical signs resolved spontaneously by 6 months of age.

Effect of a ventral slot procedure and of smooth or positive-profile threaded pins with polymethylmethacrylate fixation on intervertebral biomechanics at treated and adjacent canine cervical vertebral motion units.

OBJECTIVE: To investigate the biomechanics of cervical vertebral motion units (VMUs) before and after a ventral slot procedure and after subsequent pin-poly-methylmethacrylate (pin-PMMA) fixation and to assess the use of smooth and positive-profile threaded (PPT) pins in pin-PMMA fixation and intravertebral pin placement. SAMPLE POPULATION: Cervical portions (C3 through C6 vertebrae) of 14 cadaveric canine vertebral columns. PROCEDURE: Flexion and extension bending moments were applied to specimens before and after creation of a ventral slot across the C4-C5 intervertebral space and after subsequent smooth or PPT pin-PMMA fixation at that site. Data for the C3-C4, C4-C5, and C5-C6 VMUs were compared among treatments and between pin types, and pin protrusion was compared between pin types. RESULTS: Compared with values in intact specimens, ventral slot treatment increased neutral zone range of motion (NZ-ROM) by 98% at the treated VMUs and appeared to decrease overall ROM at adjacent VMUs; pin-PMMA fixation decreased NZ-ROM by 92% at the treated VMUs and increased overall NZ-ROM by 19% to 24% at adjacentVMUs. Specimens fixed with PPT pins were 82% (flexion) and 80% (extension) stiffer than smooth-pin-fixed specimens. Overall, 41% of pins protruded into foramina; PPT pins were more likely to protrude into transverse foramina. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that fixation of a cervical VMU alters the biomechanics of adjacent VMUs and may contribute to intervertebral degeneration of adjacent intervertebral disks. Use of threaded pins may lower the incidence of pin loosening and implant failure but enhances the likelihood of transverse foramina penetration.