Spine Health & Spinal Hygiene

Most of us have heard the term spinal tap, or have seen it on a tv medical drama show. It is known as a lumbar puncture, but what does this procedure involve and how is it utilized? What to know. This procedure is performed in the lower part of the back. It can be used for:

• Health diagnosis
• Medication administration
• Imaging assistance

A spinal tap is performed by a doctor or nurse trained to do lumbar punctures. A specialized needle is inserted between the vertebrae to collect cerebrospinal fluid. Cerebrospinal fluid is a watery, colorless fluid that cushions the spinal cord and brain, protecting them from injury/damage. Questions may arise as to when an individual would need a spinal tap, how dangerous it is, and what to expect from this procedure?

Spinal Tap Utilization

Spinal taps are often utilized in helping to diagnose infections of the central nervous system. One of the most common infections is meningitis. A sample of cerebrospinal fluid is taken, tested, and if infectious organisms are growing within, these are clue/s for determining and customizing a treatment plan and antibiotic therapy. The procedure also helps with:

• Identifying central nervous system disorders, like multiple sclerosis, or epilepsy for example.
• Diagnosing cancers that affect the brain or spinal cord
• Administration of chemotherapy or anesthesia

Spinal taps are also used with imaging assistance.

For example, a contrast dye can be injected into the cerebrospinal fluid to get an anatomical view of the spinal cord and coverings. They are quite helpful when an individual cannot have an MRI done.

A spinal tap is done in a hospital or outpatient facility, depending on the reason for the tap. It is not an emergency procedure. Emergencies bring to mind situations and events that have to be done within seconds/minutes. A lumbar puncture does not entail that type of action.

Preparation

Listen and follow the provider’s instructions regarding what to eat and drink.

• An individual could be told to not eat or drink anything for a specific set of hours before.
• Any prescription/s, over-the-counter meds, and drug allergies need to be disclosed to the medical team that will perform the procedure.
• Individuals can wear their own clothes but preferably loose-fitting and comfortable should be the objective.
• Once at the location a hospital gown is given to the patient for the procedure.
• The day of the appointment, tell the doctor of any unusual symptoms.
• Have a designated driver for the ride home, as sometimes a patient can feel weak and dizzy after the procedure.

The Procedure

A tap is a simple procedure that usually takes a half-hour or less to complete.

• The patient sits bent forward or lying down on the side.
• The knees should be pulled up as far as possible with the chin down into the chest curled into a ball.
• This arcs the back and spaces out the vertebrae, so there is a wider area for the needle to enter.
• The skin is cleaned with an antiseptic.
• A sterile sheet or towel is placed over the patient that has an opening exposing the lower back.
• Local anesthesia is injected to numb the area.
• Unless the doctor instructs movement, remaining still is key as the advancement of the needle into the small area is a delicate procedure.
• There is an initial what feels like a stinging sensation, but the patient does not feel the actual needle as it advances.
• The needle gets inserted into the spinal space where the cerebrospinal fluid resides.
• The cerebrospinal fluid pressure is measured.
• Sometimes an ultrasound or specialized x-ray technique, known as fluoroscopy is used to locate the best place for the needle.
• This is where the reason for the tap determines what action is taken. Either medicine is administered or a small amount of cerebrospinal fluid is taken.
• The needle is retracted.
• A bandage is applied.
• Spinal tap pain is rare, but sometimes the needle can brush a nerve root when it is inserted. It could feel like an electric shock down the leg.

Recovery

Once finished, the patient lies on their back for 30 to 60 minutes so the doctor can check for any abnormalities or affects. Being sent home depends on the reason for the tap. If there is unexplained fever, nausea, etc, a patient will not be sent home.

If it was an outpatient procedure the patient can leave and resume some simple activities after having a few hours of relaxation. Temporary pain meds are prescribed to address any discomfort. Results could come a day or a week later. They depend on the reason for the spinal tap.

Risks and Complications

It is considered a safe procedure with rare complications. The most common effect is a headache and usually comes on several hours, to a day or two later. These will not lead to any neurologic problems. Water or tea can help prevent and reduce the headache. Over-the-counter pain relievers can help too. However, if the headache continues after two days, call the doctor. A very small possibility of a more severe complication could happen including:

• Infection
• Bleeding
• Numbness
• Brain herniation or movement of the brain tissue from the added pressure
• Nerve or spinal cord damage

This is a very safe procedure with the medical team being highly trained and skilled professionals that are careful and gentle.

Auto Accident Doctors & Chiropractic Treatment

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The scope of our information is limited to chiropractic, musculoskeletal, physical medicines, wellness, and sensitive health issues and/or functional medicine articles, topics, and discussions. We use functional health & wellness protocols to treat and support care for injuries or disorders of the musculoskeletal system. Our posts, topics, subjects, and insights cover clinical matters, issues, and topics that relate and support directly or indirectly our clinical scope of practice.*

Our office has made a reasonable attempt to provide supportive citations and has identified the relevant research study or studies supporting our posts. We also make copies of supporting research studies available to the board and or the public upon request. We understand that we cover matters that require an additional explanation as to how it may assist in a particular care plan or treatment protocol; therefore, to further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900. The provider(s) Licensed in Texas& New Mexico*

Summary

• Neoplasms
• The vast majority of clinically suspected bone Mets are found in the axial skeleton and proximal femurs/humeri
• Radiography is the most cost-effective and readily available initial imaging tool to investigate bone Mets but often fails early metastatic detection
• Tc99 bone scintigraphy is the most sensitive and cost-effective imaging modality to demonstrate metastatic foci
• MR imaging may help  regional identification of bone Mets especially if x-radiography is unrewarding
• Significant limitations of MRI: inability to perform a whole-body MRI scan
• Cost and other contraindications such as cardiac pacemakers and cochlear implants may be another limiting factor

Marrow Based Neoplasms

• Malignancy originating from the marrow cells are often referred to as "round-cell tumors."
• Multiple Myeloma (MM)
• Lymphoma
• Ewing's sarcoma
• The last two are less frequent than MM

• Red marrow in adults is in the axial skeleton and proximal femurs/humeri d/t gradual marrow "retraction" following the childhood

• Note bone marrow biopsy histopathology specimen of MM with abnormal plasma cells replacing regular marrow residents (above image)
• Multiple Myeloma (MM) is the most common primary bone neoplasm in adults>40s. Etiology is unknown, but many theories exist (e.g., genetic, environmental, radiation, chronic inflammation, MGUS)
• MM: malignant proliferation of plasma cells >10% of red marrow, with subsequent replacement of normal marrow cells by myeloma cells and overproduction of monoclonal antibodies paraproteins (M protein) with heavy chains IgG (52%), IgA (21%), IgM (12%) and light chains kappa or lambda aka Bence-Jones proteins

Clinical Presentation of MM

• MM is occasionally detected as unexplained anemia on routine blood studies for unrelated complaints
• Common MSK symptoms: Bone pain/Pathologic fractures
• Constitutional: Weakness/malaise
• Systemic: bleeding, anemia, Infection (especially pneumococcal) d/t marrow replacement and pancytopenia
• Hypercalcemia d/t bone resorption
• Renal failure aka myeloma kidney
• Neuropathies
• Amyloidosis
• Gout
• Diagnostic imaging plays an essential role during the Dx of MM
• Bone marrow aspiration biopsy, blood tests, and serum protein electrophoresis may be used 
• Imaging approach: bone pain is investigated with initial x-radiographs if radiographs are unrewarding MR imaging may help to reveal bone marrow abnormality. MRI is recommended as myeloma survey
• Currently, MRI protocol known as "whole body myeloma scan" consisting of T1, T2-fat suppressed, and T1+C coronal sequences can detect MM in the skull, spine, pelvis, ribs and femurs/humeri. This technique is much more superior to radiographic "skeletal myeloma survey."
• Tc99 bone scintigraphy is not typically used for MM because over 30% of MM lesions are "cold" or photopenic on radionuclide bone scan d/t highly lytic nature of MM with osteoclasts outpacing osteoblasts.
• A radiographic skeletal survey is considered more sensitive than bone scintigraphy in MM
• PET-CT scanning of MM is gaining popularity due to the high level of detection of multiple sites of MM

• Radiographic Dx of MM: consists of identification of characteristically localized focal osteolytic "punched out" or "moth-eaten" lesions of variable sizes following the distribution of adults red marrow
• Note rad abnormality is known as "raindrop skull" is characteristic of MM

• Radiographic appearance of MM may vary from "punched out" round radiolucencies to "moth-eaten" or permeating osteolytic lesion producing endosteal scalloping (yellow arrow)

• Pelvis and femurs are commonly affected by MM and present radiographically as round lytic punched out or moth-eaten lesions
• N.B. Occasionally MM may pose radiographic dilemma by presenting as generalized osteopenia in the spine that can be difficult to differentiate from age-related osteoporosis

• MR imaging of MM reveals  marrow changes with low signal on T1, a high signal on fluid-sensitive sequences and bright contrast enhancement on T1+C gad d/t increased vasculature and high activity of  MM cells

• Example of full-body MRI of "whole body myeloma scan" with T2-fat suppressed (A), T1 (B) and T1+C (C) pulse sequences produced in coronal slices
• Note multiple foci of bone marrow changes in the spine pelvis and femurs

Miscellaneous Neoplasms of the Spinal Column

• Chordoma: is relatively uncommon but considered the m/c primary malignant neoplasm that only affects the spine. D/t slow growth is often misdiagnosed for a considerable length of time as LBP
• Pathology: derives from malignant transformation of notochordal cells presented as mucoid, gelatinous mass containing physaliphorous cells
• Demo: M: F 3:1 (30-70S). 50%-sacrococcygeal, 35% spheno-occipital 15%-spine
• Clinically: asymptomatic for a long time until non-specific LBP, changes in bladder & bowel, neurological signs are less common d/t midline "outward" growth & inferior to S1. Local invasion worsens prognosis. 60%-survive 5-years, 40%-10-years, Mets are delayed, poor prognosis d/t local invasion. >50% can be id. on DRE.
• Imaging: x-rays often tricky d/t overlying gas/feces. CT is >sensitive to id the bone mass and internal calcifications. MRI: T2 bight signal, T1 heterogeneously low and high d/t mucus/blood decomposition, MRI best detects local invasion and essential for care planning. Rx:  complete excision is often impossible d/t local vascular invasion.

• Giant cell tumor (GCT): 2nd most common primary sacral tumor. It is a histolgically benign neoplasm containing multinucleated Giant cells of Monocyte-Osteoclast origin
• Imaging Dx: x-radiography is the 1st step usually in response to complaints of LBP. Often challenging to id on x-rays d/t bowel gas/feces
• Key rad feature: osteolytic expansile lesion noted by destruction of sacral arcuate lines. CT may id the lesion better. MRI is the modality of choice folowing x-rays. MRI: T1 low to intermediate signal. Heterogeneously high d/t edema with areas of low signal on T2 d/t blood degradation and fibrosis. Characteristic fluid-fluid levels may be noted especially if ABC develops within a GCT. Rx: operative. Prognosis is less favorable than GCT in long bones d/t lung Mets (deposits) in 13.7%

• Aneurysmal Bone Cysts (ABC) are benign expansile tumor-like bone lesions (not a true neoplasm) composed and filled with numerous blood-filled channels. Thus the term "blood sponge." ABC is m/c id in children and adolescents
• Unknown etiology: trauma and pre-existing bone neoplasm (e.g., GCT) often reported. Clinically: pain that may be progressive d/t rapid nature of ABC expansion. In the spine, ABC m/c affects posterior elements and presented as expansile, soap-bubbly or lytic lesion.
• DDx: can be broad, but Osteoblastoma and GCT are the top DDxs.
• Imaging: x-rays demo expansile mass in posterior elements, CT is more sensitive than x-rays, MRI will demo characteristic fluid-fluid levels and mixed high and low signal d/t edema and blood decomposition/aging with some septations.
• N.B. MRI fluid-fluid levels are not exclusive to ABC, and DDx includes GCT, osteoblastoma, telangiectatic osteosarcoma.
• Rx: operative curettage and bone grafting, fibrosing agents. Recurrence 10-30%.

Spinal Neoplasms

Additional Resources

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931792/
• https://emedicine.medscape.com/article/1267223-overview#a4
• https://www.ncbi.nim.nih.gov/pmc/articles/PMC2958273/
• http://bonetumor.org/

• Spinal Arthritis
• Ossification of Posterior Longitudinal Ligament (OPLL). Less frequent than DISH.
• Greater clinical importance d/t spinal canal stenosis and cervical myelopathy
• Asian patients are at higher risk
• Both OPLL & DISH may co-exist and increase the risk of Fx
• Imaging: x-rad: linear radioopacity consistent with OPLL
• Imaging modality of choice: CT scanning w/o contrast
• MRI may help  to evaluate myelopathy
• Care: surgical with laminoplasty (above right image) that has been pioneered and advanced in the Far East

M/C Inflammatory Arthritis In Spine

• Rheumatoid spondylitis (Rheumatoid arthritis) d/t inflammatory synovial proliferation pannus rich in lymphocytes, macrophages, and plasma cells
• C/S RA may affect 70-90% of patients
• Variable severity from mild to destructive disabling arthropathy
• RA IN C/S m/c affects C1-C2 due to an abundance of rich synovial tissue
• Typically infrequent in the thoracic/lumbar region
• Sub-axial C/spine may be affected later due to facets, erosions, ligament laxity and instability showing "Stepladder" appearance
• Clinically: HA, neck pain, myelopathy, etc. inc. Risk of Fx/subluxation. Any spinal manipulation HVLT ARE STRICTLY CONTRAINDICATED.
• Rx: DMARD, anti-TNF-alfa, operative for subluxations, etc.

Rheumatoid Spondylitis C1-C2. Perform X-radiography initially with flexed-extended views. Note Dens erosion, C1-2 subluxation (2.5 mm) that changes on mobility 

• RA spondylitis: an erosion of the odontoid with the destruction of C1-C2 ligaments and instability
• Stepladder aka Step-step sub-axial deformity d/t facets erosions and ligamentous destruction/laxity
• MRI required to evaluate cord compression/myelopathy 

• Sagittal T2 WI MRI of pt with RA. Rheumatoid pannus formation is present at C1-2 (arrow) causing mild cord compression
• RA pannus may develop early before frank x-radiography changes noted
• Clinically: HA, neck pain, tingling in UE, positive Lhermitte phenomenon d/t cervical myelopathy

Operative Care of Rheumatoid Spondylitis and Its Complications

Seronegative Spondyloarthropathies

• Ankylosing Spondylitis (AS)
• Enteropathic Arthritis (EnA) (d/t IBD: Crohn's & UC) identical to AS on imaging
• Psoriatic Arthritis (PsA)
• Reactive Arthritis (ReA)
• All share the following features: m/c HLA-B27 marker, RF-, Sacroiliitis, Enthesitis, Ocular Involvement (i.e., conjunctivitis, uveitis, episcleritis, etc.)
• AS & EnA are radiographically virtually indistinguishable, but EnA typically presents with less severe spinal changes than AS
• Both PsA & ReA present with virtually identical spinal changes, but ReA typically affects the lower extremity compared to PsA affecting hands and feet

• AS: likely autoimmune systemic inflammatory disease that targets SIJ, spinal facet joints annuls of the disc, rib joints and all spinal ligaments.
• Key path feature: enthesitis.
• Extraspinal features: uveitis, aortitis, pulmonary fibrosis, amyloidosis, cardiovascular disease.
• M:F 4:1, age: 20-40 m/c. Clinic LBP/stiffness, reduced rib expansion <2 cm is > specific than HLA-B27, progressive kyphosis, risk of Fx's.
• Imaging steps: 1st step-x-rays to id. Sacroiliitis/spondylitis. MRI & CT may help if x-rays are unrewarding.
• Labs: HLA-B27, CRP/ESR, RF-
• Dx: clinical+labs+imaging.
• Rx: NSAID, DMARD, anti-TNF factor therapy
• Key Imaging Dx: always presents initially as b/l symmetrical sacroiliitis that will progress to complete ankylosis. Spondylitis presents with continuous ascending discovertebral osteitis (i.e., marginal syndesmophytes, Romanus lesion, Anderson lesion), facets and all spinal ligament inflammation and fusion with a late feature of "bamboo spine, trolley track, dagger sign," all indicating complete spinal ossification/fusion. Increasing risk of Fx's. 

Key Dx of Sacroiliitis

• Blurring, cortical indistinctness/irregularity with adjacent reactive subchondral sclerosis initially identified primarily on the iliac side of  SIJs.
• Normal SIJ should maintain a well defined white cortical line. Dimension 2-4 mm. May look incongruous d/t 3D anatomy masked by 2D x-rays. 

Key Imaging Dx In Spine

• Marginal syndesmophytes and inflammation at the annulus-disc (above arrows) at the earliest dx; by MRI as marrow signal changes on T1 and fluid sensitive imaging (above top images). 
• These represent enthesitis-inflammation that will ossify into bamboo spine.
• Lig ossification: trolley track/dagger sign

• AS in extraspinal joints: root joints, hips, and shoulders
• Symphysis pubis
• Less frequent in peripheral joints (hands/feet)
• All seronegatives may present with heel pain d/t enthesitis

• Complication: Above Carrot-stick/chaulk-stick Fx

• PsA & ReA (formerly Reiter's) present with b/l sacroiliitis that virtually identical to AS
• In the spine PsA & ReA DDx from AS by the formation of non-marginal syndesmophytes aka bulky paravertebral ossifications (indicate vertebral enthesitis)
• For a clinical discussion of Spondyloarthropathies refer to:
• https://www.aafp.org/afp/2004/0615/p2853.html

Spinal Arthritis

Hyperextension Injury

• Hangman's Fx aka traumatic spondylolisthesis of C2 with a fracture of pars interarticularis or pedicles (unstable)
• MVA is the most common cause
• Mechanism: acute hyperextension of upper C/S similar to judicial hanging (never actually seen and most deaths are due to asphyxiation)
• Secondary flexion may tear PLL and disc
• Associated injuries: 30% have other c-spine fx especially Extension teardrop at C2 or C3 due to avulsion by ALL
• Cord paralysis may only present in 25% due to bony fragments dissociation and canal widening
• Hangman fx and extension teardrop
• Cervical degeneration and previous fusion is a key predisposing factor due to the lack of mobility and suppleness, rendering C/S easy to fracture
• Imaging: initial x-radiography then CT that helps to delineate another injury such as facet/pedicle Fx further. MRI may help if complicated by Vertebral A. damage
• Management: if type 1 injury then closed reduction and rigid collar for 4-6 weeks, halo bracing if type 2 (>3-5mm displacement) Fx/instability, anterior or posterior spinal fusion at C2-3 if type 3 Fx (>5-mm displacement)

• Extension teardrop Fx (stable) potentially unstable if put in extension
• Avulsion of an inferior anterior body by ALL. More seen in elderly with superimposed C/S spondylosis
• Key radiography: a smaller anterior-inferior body corner, no disruption of ligamentous alignment. Typically at C2 or C3 due to sudden hyperextension and ALL avulsion
• Complication: central cord syndrome (m/c incomplete cord injury) esp. in superimposed spondylosis and canal stenosis by the laxity of ligamentum flavum and osteophytes
• Management: hard collar isolation 

Vertical (axial) Compression Injury

• Jefferson Fx (named after British neurosurgeon who defined it) (unstable but neurologically intact Fx) 7% of all C/S injuries. Stability is dependent if the transverse ligament is intact or torn, which can be noted by overhanging of C1 lateral masses over C2 >5-mm combined (left image)
• Mechanism: C1 compression (e.g., diving into shallow waters) causing burst Fx-classically 4-parts of the anterior and posterior arch of C1. Variations exist.
• Complications: 50% show other C/S Fx, 40% show Odontoid C2 Fx esp. if extension and axial loading occur

• Imaging: x-radiography followed by CT scanning to evaluate subaxial injury and complexity of C1 injury. Note Jefferson Fx with pillar and transverse foramina fx requiring posterior occipital-cervical fusion (below right image).
• Management: rigid collar immobilization if the transverse ligament is intact. Halo brace or fusion if the transverse ligament is ruptured 

Cervical Injuries With Variable Mechanisms of Trauma

• Odontoid process fractures:
• These occur with a variety of mechanisms, flexion, extension, lateral flexion. Elderly with superimposed spondylosis are at higher risk.
• Anderson & D'Alonzo classification (below). Type 2 is the most common and most unstable. Type 3 has the best chance of healing d/t more massive bleed into C2 body and better healing potential.
• Imaging: x-radiography can miss some Fx. CT scanning is essential.
• On x-radiography note tilting of the Dens on lateral and APOM views. CT will reveal the injury and classify it.
• Complications: cord injury, non-union

• CT scanning: type 2 odontoid fracture (unstable)
• Management: type 1 (alar ligament avulsion) most stable observed and treated with rigid collar.
• In young patients, Halo brace is used to treat type 2
• Older patients do not tolerate Halo
• Operative C1-2 fusion if unstable is Dx and cord signs or other complicating factors are present

Normal Radiographic Variants & Anomalies Simulating Pathology

• Pediatric spine appears different especially in children younger than 10-years old.
• Normal variations; ADI 5-mm and may increase or decrease on flexed/extended views by 1-2-mm
• C2-3 may appear as pseudo-subluxation due to normal ligamentous laxity in children (below arrow)
• Pediatric vertebral bodies usually are narrower and anteriorly wedged due to the presence of cartilaginous tissue

• APOM view appears different in children, and some asymmetry of C1 articular masses is normal (below top image) and should not be confused with Jefferson Fx
• In adults, any asymmetry or "overhanging" of C1 articular masses is pathological and may indicate Jefferson fx

• Standard ossification centers of the Atlas synchondrosis in children should not be mistaken for fractures

• Persistent ossiculum terminal of Bergman is a typical variant/anomaly of tenacious un-united ossification center and should not be confused with type odontoid fx

• Os odontoideum
• Un-united growth center that currently considered as an un-noticed injury that disturbed normal growth in a child younger than 5-years-old
• It may be a cause of C1-2 instability and should be evaluated with flexed and extended cervical views
• Should not be confused with type 2 Dens fracture because it typically more demonstrates greater mineralization of bone

• Incomplete bilateral agenesis of the C1 posterior arch
• Anomalous closure of C1 posterior arch
• Should not be confused with a fracture
• However, local or cord symptoms may develop after trauma in some cases
• Relatively rare anomaly developing due to failed chondrogenesis and ossification of posterior ossification centers of the Atlas

• Patients with Down syndrome may suffer from increased ligamentous laxity and other abnormalities
• Increased risk of subluxation at C1-2

• Burst Fx (unstable) 2-columns are damaged
• Mechanism: axial loading with frequent flexion after falls and MVAs
• The thoracolumbar region is the most vulnerable due to the increased fulcrum of motion
• Key radiography: acute compression fracture and collapse of body height, retropulsion of posterior body and acute kyphotic deformity on the lateral view
• On the frontal view: interpedicular widening (below yellow arrow), regional soft tissue swelling (below green arrow)

• Imaging: x-radiography should be followed by CT scanning w/o contrast
• MRI if neurologically unstable due to cord or conus injury
• Complications: cord damage by acutely retropulsed bone fragments
• Management: non-operative if neurologically intact and <50% body retropulsed with minimal kyphosis
• Operative (fusion) if 50% or more body retropulsed, laminar/pedicle Fx, neuro compromised

18-Year Old Female Following Trampoline Accident

• AP & lateral L/S views
• Note acute compression fracture, a vertebral body extending to posterior elements
• Widening of the inter-spinous distance between T11-T12 (below arrow)
• Radiolucent fracture line is seen through the T12 body on the AP projection
• CT scanning was performed

• Sagittal reconstructed Thoracic and Lumbar CT slices in bone window
• Note acute compression fracture, the T12 body extending into pedicle and lamin
• Dx: Chance fracture of T12
• MR imaging was performed

• T2 Wl sagittal MRI
• Findings: acute compression fracture T12 body extending to posterior elements causing rapture of interspinous and flavum ligaments
• Mild compression of the distal cord above the conus is noted with a minimal signal abnormality
• Dx: Chance fracture

• Chance Fx aka (Seatbelt Fx) - is a flexion-distraction injury (unstable)
• M/C in lower thoracic-upper lumbar
• All 3-columns fail: column 3 torn by distraction, columns 1 and 2 fail on compression (Denis classification)
• Causes: MVA, falls
• Imaging: initial x-radiography should be followed by CT scanning w/o contrast to assess bone fragments retropulsion/canal compression. MRI may help to evaluate potential cord damage and ligaments tearing
• Management: non-operative immobilization if neuro intact
• Operative decompression and fusion

Spinal Trauma Imaging Approach

Resources:

• https://emedicine.medscape.com/article/824380-overview
• https://emedicine.medscape.com/article/248236-overview#a9
• https://emedicine.medscape.com/article/397896-overview#a3
• https://www.aafp.org/afp/1999/p331.html

Following upper limb peripheral nerve transection and surgical repair, some patients regain good sensorimotor function while others do not. Understanding peripheral and central mechanisms that contribute to recovery may facilitate the development of new therapeutic interventions. Plasticity following peripheral nerve transection has been demonstrated throughout the neuroaxis in animal models of nerve injury. However, the brain changes that occur following peripheral nerve transection and surgical repair in humans have not been examined. Furthermore, the extent to which peripheral nerve regeneration influences functional and structural brain changes has not been characterized. Therefore, we asked whether functional changes are accompanied by grey and/or white matter structural changes and whether these changes relate to sensory recovery? To address these key issues we (i) assessed peripheral nerve regeneration; (ii) measured functional magnetic resonance imaging brain activation (blood oxygen level dependent signal; BOLD) in response to a vibrotactile stimulus; (iii) examined grey and white matter structural brain plasticity; and (iv) correlated sensory recovery measures with grey matter changes in peripheral nerve transection and surgical repair patients. Compared to each patient’s healthy contralesional nerve, transected nerves have impaired nerve conduction 1.5 years after transection and repair, conducting with decreased amplitude and increased latency. Compared to healthy controls, peripheral nerve transection and surgical repair patients had altered blood oxygen level dependent signal activity in the contralesional primary and secondary somatosensory cortices, and in a set of brain areas known as the ‘task positive network’. In addition, grey matter reductions were identified in several brain areas, including the contralesional primary and secondary somatosensory cortices, in the same areas where blood oxygen level dependent signal reductions were identified. Furthermore, grey matter thinning in the post-central gyrus was negatively correlated with measures of sensory recovery (mechanical and vibration detection) demonstrating a clear link between function and structure. Finally, we identified reduced white matter fractional anisotropy in the right insula in a region that also demonstrated reduced grey matter. These results provide insight into brain plasticity and structure-function-behavioural relationships following nerve injury and have important therapeutic implications.

Keywords: cortical thickness; fMRI; diffusion tensor imaging; plasticity; peripheral nerve injury
Abbreviations: BA=Brodmann area; BOLD=blood oxygen level dependent; fMRI=functional magnetic resonance imaging;
PNIr=peripheral nerve transection and surgical repair; S1=primary somatosensory cortex; S2=secondary somatosensory cortex

Introduction

Following upper limb peripheral nerve transection and surgical repair (PNIr), �25% of patients have not returned to work 1.5 years after surgery (Jaquet et al., 2001). In addition, �57% of patients with nerve injuries are between 16–35 years of age (McAllister et al., 1996); thus, a long life of disability and economic difficulties may accompany upper limb nerve transection. Understanding the central and peripheral ramifications of peripheral nerve injury may facilitate the development of new therapeutic strategies and intervention programs.

It is not known how the brain responds to PNIr in humans. However, animal studies have established that plasticity within the somatosensory cortex begins immediately following peripheral nerve transection, and that 1 year after complete nerve transection and surgical repair, cortical maps contain patchy, non- continuous representations of the transected and adjacent nerves (Wall et al., 1986). The mechanisms that facilitate functional plasticity are thought to include the immediate unmasking of pre-existing projections from adjacent cortical and subcortical levels, and long term sprouting of axons at multiple levels of the neuroaxis, including the primary somatosensory cortex (S1) (Florence and Kaas, 1995; Hickmott and Steen, 2005).

Human brain imaging studies have corroborated the findings from animal models with the identification of altered functional MRI activation maps due to spinal cord injury, amputation, toe- to-thumb transfer, and in patients with carpel tunnel syndrome (Lotze et al., 2001; Manduch et al., 2002; Jurkiewicz et al., 2006; Napadow et al., 2006). Furthermore, structural MRI studies have recently visualized grey and white matter changes following traumatic injuries and in diverse pathological conditions, including limb amputation and chronic pain (Apkarian et al., 2004; Draganski et al., 2006; Davis et al., 2008; Geha et al., 2008; May, 2008). Grey matter changes are thought to be related to changes in cell size, atrophy and/or loss of neurons or glia, whereas white matter changes are impacted by axonal degenera- tion and loss of myelin (Beaulieu, 2002; May, 2008).

A powerful approach to delineate mechanisms of pathology and plasticity is to combine functional and structural grey and white matter imaging techniques. We previously reported that patients with complete upper limb PNIr retained profound somatosensory deficits that persist 41.5 years following surgery (Taylor et al., 2008a). Based on these findings, we reasoned these patients would exhibit functional and structural brain changes in key somatosensory brain areas. Therefore, in this study, we hypothesized that PNIr patients would have: (i) reduced blood oxygen level dependent (BOLD) responses to vibratory stimulation of the transected nerve territory, in the region of S1 that represents the injured upper limb and in the secondary somatosensory cortex (S2); (ii) a corresponding reduction in cortical thickness in these regions of the contralesional S1 and S2; (iii) a correlation between changes in cortical thickness and psychophysical measures of somatosensory function (vibration and touch detection thresh- olds); and (iv) reduced fractional anisotropy (a measure of white matter integrity) in white matter feeding into/out of these somatosensory cortical areas.

Methods

Subjects

We recruited 27 patients with complete transection of the median and/or ulnar nerve followed by surgical repair from plastic surgeons affiliated with the University of Toronto Hand Program between June 2006 and May 2008. From this larger cohort, 14 pain-free patients (three females, 11 males; 34 � 10 years) with complete transection of the right median and/or ulnar nerve were included in the study [to avoid confounds related to the presence of pain and laterality patients with pain (n=6) and left sided lesions (n=7) were excluded from this analysis]. All patients underwent microsurgical nerve repair at least 1.5 years prior to study enrolment (recovery time varied from 1.5 to 8 years). In addition, we recruited 14 age- and sex-matched healthy controls (3 females, 11 males; 34 � 10 years). All subjects gave informed written consent to procedures approved by the University Health Network Research Ethics Board. All subjects were right handed (determined using the Edinburgh handedness inventory: Oldfield, 1971) and had no history of neurological injury or chronic pain (either before or after nerve transection). See Table 1 for demographic details.

Study Design

All subjects participated in an imaging session that included: (i) functional magnetic resonance imaging (fMRI) in response to vibrotactile stimuli applied to the right index finger (within the median nerve territory); (ii) a high-resolution anatomical scan of the whole brain, acquired for image registration and for the analysis of cortical grey matter; and (iii) two diffusion tensor imaging scans for the assessment of white matter integrity. Prior to imaging, subjects were instructed in the basic design of the experiment and reminded to remain as still as possible throughout the duration of the scan.

Subjects were free to withdraw from the study at any time. In addition, a sensory and motor assessment was performed for all subjects (Taylor et al., 2008a). As touch and vibration detection thresholds were correlated with cortical thickness a description of these methods is included below (other psychophysical measures will be reported elsewhere).

Vibration Threshold

Vibration detection thresholds were determined using a hand held Bio-Thesiometer (Bio-Medical Instrument Company, USA). The device has a 12-mm probe that was placed on the distal phalanx of the right index finger (D2). Thresholds were determined using the method of limits: the amplitude (voltage) was gradually increased until the subject indicated that they perceived the stimulus. Vibration thresholds were acquired three times and an average value was calculated. During vibration threshold testing, subjects were instructed to close their eyes and rest the back of their hand on a supportive cushion.

Mechanical Detection Threshold

Mechanical detection thresholds were determined using a standardized set of von Frey filaments (OptiHair2 Marstock Nervtest, Germany) containing 12 logarithmically spaced calibrated filaments that delivered forces from 0.25–512 mN. The contact surface diameter of all 12 filaments was ~0.4mm. Trials were conducted with the subject’s eyes closed and hands resting on a soft cushion. Probes were applied in an ascending series and subjects were required to make a response every time they felt a probe touch the right D2 fingertip. This process was repeated three times. The force for the filament that was detected in at least two of three trials was reported as that subject’s mechanical detection threshold.

Nerve Conduction Testing

Patients participated in bilateral sensory and motor nerve conduction studies at the Toronto Western Hospital electromyography (EMG) clinic. For motor nerve conduction, the stimulating electrode was placed at the wrist and elbow (separately) and the recording electrode was placed over the abductor pollicis brevis, for median nerve assessment, or the abductor digiti minimi for ulnar nerve assessment. For sensory nerve testing the recording electrode was placed at the wrist and the stimulating electrode was placed at digits D2, D3 and D5. A senior, experienced neurologist from the Toronto Western Hospital EMG Clinic (Dr Peter Ashby) reviewed all clinical assessments to deter- mine which nerves demonstrated normal/abnormal responses. As amplitude and latency measures are known to vary substantially between subjects (due to factors such as the density of innervation, the depth of the nerve and the thickness of an individual subject’s skin) (Kimura, 2001) each patient’s untransected nerve served as their own control for comparison with values from the transected side. In those patients with detectable nerve conduction responses, paired t-tests were performed to assess the difference in latency or amplitude measures between each patient’s transected and contralesional untransected nerves.

Imaging Parameters

Brain imaging data were acquired using a 3T GE MRI system fitted with an eight-channel phased array head coil. Subjects were placed supine on the MRI table and each subjects’ head was padded to reduce movement. Whole-brain fMRI data was acquired using echo planar imaging (28 axial slices, field of view (FOV) = 20 x 20 cm, 64 x 64 matrix, 3.125 x 3.125 x 4mm voxels, echo time (TE) = 30 ms, repetition time (TR) = 2000 ms). The scan time was 5 min and 8 s (154 frames). During scanning, a non-painful, 12 Hz vibrotactile stimulus was applied to the distal phalanx of the right D2 using balloon diaphragms driven by compressed air (Device man- ufactured by Dr Christo Pantev; www.biomag.uni-muenster.de). Stimuli were delivered in blocks of 10s interleaved with 20s of rest, for a total of 10 blocks of stimulation and 10 blocks of rest. The first 8 s (4 TRs) of data acquired from each run were discarded to allow for fMRI signal equilibration. Subjects were instructed to keep their eyes closed throughout scanning and focus on the stimuli. A whole brain three dimensional (3D) high-resolution anatomical scan (124 sagittal slices, 24 x 24 cm FOV, 256 x  256 matrix, 1.5 x 0.94 x 0.94 mm voxels) was acquired with a T1-weighted 3D spoiled gradient echo sequence (one signal average, flip angle = 20� , TE �5 ms). In addition, two diffusion tensor imaging scans (38 axial slices, FOV 24 x 24 cm, 128 x 128 matrix, 1.875 x 1.875 x 3 mm voxels) were acquired along 23 directions with a b-value of 1000smm–2. Each run also contained two volumes with no diffusion weighting.

fMRI Analysis

Data were analysed using Brainvoyager QX v1.8 (Brain Innovaton, Maastricht, Netherlands). Pre-processing included: 3D motion correction, slice scan-time correction, linear trend removal, high-pass filtering (five cycles per run), and spatial smoothing with a 6mm full width at half maximum (FWHM) Gaussian kernel. fMRI data sets were interpolated to 3 x 3 x 3 mm voxels, registered to the high-resolution ana- tomical image, and normalized to standard Talairach space (Talairach and Tournoux, 1988). Voxels are reported as 1 x 1 x 1 mm. Data were analysed using the general linear model; the model was obtained by convolving the boxcar function of the time course of tactile stimulation with the standard haemodynamic response function. To identify between group differences in activation patterns a fixed effects analysis was performed with the contrasts: (i) healthy controls: stimulation 4 rest; (ii) PNIr: stimulation 4 rest; and (iii) healthy controls 4 PNIr. Activation maps were thresholded at a corrected value of P50.05 (derived from an uncorrected P50.0001 and 120mm3 contiguous voxels as previously reported: Taylor and Davis, 2009); this was also validated by running a Monte Carlo Simulation with AlphaSim application implemented in the Analysis of Functional Neuroimage (AFNI) software. This analysis included only the 11 patients that sustained transection of the right median nerve (n=9) or the right median and ulnar nerve (n = 2) (i.e. the three patients with a pure right ulnar nerve transection were not included in this analysis).

Cortical Thickness Analysis

Cortical thickness analysis was performed using Freesurfer (http:// surfer.nmr.mgh.harvard.edu); methods have been outlined in detail elsewhere (Dale et al., 1999; Fischl et al., 1999a, b; Fischl and Dale 2000). Briefly, high-resolution T1-weighted anatomical data sets were registered to the Talairach atlas (Talairach and Tournoux, 1988). This was followed by intensity normalization, skull stripping and separation of the hemispheres. Subsequently, the white/grey matter (called the white surface) and grey/CSF (called the pial surface) boundaries were identified and segmented. The distance between the white and pial surfaces was then calculated at every point in each hemisphere of the brain. To identify group differences between the 14 patients and 14 age/sex-matched controls, a general linear model analysis was performed at every point on the brain. As individual’s cortical topography is inherently heterogeneous, a 5mm FWHM spatial smoothing kernel was applied prior to statistical analysis. Data are displayed at a corrected P50.05 (derived from an uncorrected P50.0075 and 102 contiguous vertices); this was calculated by running a Monte Carlo simulation with AlphaSim. A vertex represents a point on a two dimensional sheet, and, in this study, the distance between two vertices is 0.80mm2.

As patients exhibited significant deficits in somatosensory function within the transected nerve territory, we hypothesized that measures of somatosensory function (vibration and touch detection) would correlate with cortical thickness in the contralesional post-central gyrus (primary and secondary somatosensory cortices). Therefore, we performed correlation analyses in the patient group between: (i) cortical thickness and vibration detection threshold; and (ii) cortical thickness and touch detection thresholds. One patient did not complete psychophysical assessment; therefore, this analysis included 13 PNIr patients. In addition, to determine if there was a relationship between cortical thickness and recovery time a correlation analysis was also performed between these two measures. These correlation analyses were restricted to the contralesional post-central gyrus by including a mask (taken from Freesurfer’s built in atlas) in the general linear model. A Monte Carlo simulation was performed that was restricted to the number of vertices within contralesional post-central gyrus; images are displayed with a corrected P50.05 (derived from an uncorrected P50.0075 and 68 contiguous vertices).

Diffusion Tensor Imaging Analysis

Diffusion tensor image processing was performed with DTiStudio (www.MriStudio.org) and FSLv.4.0 (www.fmrib.ox.ac.uk/fsl/). Images were first realigned with the Automatic Image Registration tool implemented in DTiStudio, using the first B0 image in the first series acquired as the template. This process corrects for subject motion and eddy-current distortion. All images were then inspected visually to assess image quality and the alignment of the separate diffusion tensor imaging runs. If an artefact was detected, the slice was removed prior to calculating the average of the two separate diffusion tensor imaging runs. Individual FA maps were calculated using the DTIFIT tool implemented in FSL. Voxel-wise statistical analysis was performed to identify group differences in the mean fractional anisotropy using Tract Based Spatial Statistics; for a full description of these methods see Smith et al. (2006). Briefly, images were non-linearly registered to a target image (MNI152), the mean image was then created from all datasets and this image was subsequently thinned to represent all tracts that were common to all subjects. Each subject’s highest fractional anisotropy values were then projected onto the skeleton by searching in white matter perpendicular to each point on the white matter skeleton. A whole-brain voxel-wise statistical analysis was then performed between groups (14PNIr and 14 healthy controls) and images were whole brain corrected at P50.05. In addition, a region of interest analysis was performed in white matter tracts adjacent to the contralateral S1, thalamus and bilateral anterior and posterior insula. These regions were chosen as they have previously been implicated in aspects of somatosensation and because they correspond with regions that were identified in the fMRI and cortical thickness analysis (CTA) group analyses. Regions of interest were drawn on the white matter skeleton as follows: (i) The contralateral S1 region of interest originated medially at the junction between the white matter skeleton of the corona-radiata and the skeleton section feeding into the post- central gyrus; terminating at the end of the tract within a given slice.

In the z direction the region of interest extended from z=49 to 57; white matter tracts supplying the hand region. (ii) The contralateral thalamus region of interest was restricted to white matter tracks surrounding the posterior and medial thalamic nuclei (nuclei involved in somatosensory function), extending from z = –1 to 4. (iii) Insular regions of interest were drawn bilaterally within white matter adjacent to the anterior and posterior insula based on criteria previously published by our lab (Taylor et al., 2008b). The region of interest extended from z = 2 to 8. Fractional anisotropy values were extracted from each of these regions of interest and a multivariate analysis of variance (MANOVA) was performed using the Statistical Package for the Social Sciences v13.0 (SPSS Inc, Chicago), which included fractional anisotropy values for all six regions of interest.

Results

Table 1 provides demographic details for study participants. All 14 patients sustained a complete transection of the right median and/or ulnar nerve followed by microsurgical repair at least 1.5 years prior to study enrolment. The time from surgery to testing ranged from 1.5 to 8 years with a mean (�SD) of 4.8 � 3 years. Patients and controls did not (34 � 10 years both groups; t = 0.04; P = 0.97).

Psychophysics

Vibration thresholds were calculated from all three measurements since one-way repeated measures analysis of variance (ANOVA) indicated no significant differences between the three trials [F (25, 1)=0.227, P=0.64]. Vibration and mechanical detection thresh- olds were significantly impaired in PNIr patients compared to healthy controls (vibration: t = 4.77, P50.001, Fig. 3A; mechanical: t=3.10, P=0.005, Fig. 3D).

Nerve Conduction Testing

Amplitude and latency measures obtained from each patient’s contralesional nerves were classified as normal by an experienced neurologist at the Toronto Western Hospital EMG Clinic. Nine of the 14 patients completed nerve conduction testing. Table 2 displays the average increase/decrease latency and amplitude data for sensory nerve conduction from the wrist to the abductor pollicis brevis (median) or abductor digiti minimi (ulnar) muscles and for sensory conduction from the wrist to D2 (median) and D5 (ulnar) compared to each patients uninjured contralesional nerve. Out of nine, seven patients had transections that included the median nerve. Of these seven, one patient had no detectable response during motor testing and another patient had no detectable response during sensory testing.

In the six patients with detectable responses, motor conduction latencies were increased by 43% (t=6.2; P=0.002) and amplitudes were decreased by 38% (t=–2.6; P=0.045) when each patient’s transected nerve was compared to their non-injured side. Sensory conduction in median nerves also revealed a 26% increase in latency (t=3.9; P=0.011) and a 73% decrease in amplitude (t=–8.0; P=0.000) compared to normal contralesional nerves. In the four patients with ulnar nerve transections one patient had no detectable response during sensory nerve testing. In those patients with responses, ulnar nerve motor latencies were not significantly elevated (t = 2.8; P = 0.070); however, amplitudes were significantly decreased by 41% (t = –5.9; P = 0.010). Sensory testing of the ulnar nerve demonstrated a 27% increase in latency (t = 4.3; P = 0.049) but no significant increase in amplitude (t = 3.5; P = 0.072).

Functional Plasticity In The Primary Somatosensory Cortex

Functional MRI maps were calculated from the 11 PNIr patients with right median nerve transections (patients with ulnar nerve transections were excluded from this analysis) and 11 age- and sex-matched healthy controls. From Fig. 1A, it is clear that PNIr patients have significantly less activation, compared to healthy controls, in a region of S1 corresponding to Brodmann area 2 (BA2) (Talairach and Tournoux, 1988) and S2 (see Table 3 for details). The average event-related responses from these regions of interest highlight the attenuated BOLD response within the patients’ left BA2 and left S2 (Fig. 1B and C, respec- tively). Curiously, vibrotactile stimulation in the patients activated a more superior part of the post-central gyrus (probably BA1/3) (Talairach and Tournoux, 1988) (Fig. 1A and Table 3). An event- related average (Fig. 1D) demonstrates that healthy controls had minimal activation in this region. Furthermore, patients had significantly more activation in brain regions collectively known as the task positive network (asterisks in Fig. 1). See Table 3 for the full list of task positive brain areas activated. This network includes lateral prefrontal, lateral parietal, premotor and inferior temporal cortices (Table 3): brain areas that are activated during the performance of an attention demanding task and suppressed or inactive during rest or tasks that are not cognitively or attentionally challenging (Fox et al., 2005; DeLuca et al., 2006; Seminowicz and Davis 2007).

Reduced Grey Matter In The Primary Somatosensory Cortex Correlates With Sensory Recovery

Cortical thickness analysis in all 14 patients and 14 age/ sex-matched healthy controls revealed several loci of significant cortical thinning in the PNIr group (Fig. 2 and Table 4). Specifically, patients had a 13%–22% reduction in cortical thick- ness in the left (contralesional) S1, S2, pregenual anterior cingulate gyrus, ventrolateral prefrontal cortex and right anterior insula, anterior/posterior mid cingulate gyrus and paracentral lobule. Interestingly, the locations of grey matter thinning within the post-central gyrus coincide with the regions of reduced BOLD following vibrotactile stimulation (Table 4). Since we had prior knowledge of the patients’ sensory deficits and recovery time (i.e. time since microsurgical repair), we next asked whether the patients’ cortical thickness in the post-central gyrus correlated with their sensory mechanical and vibration detection thresholds, or with their recovery time. These analyses revealed a negative correlation between cortical thickness and vibration detection thresholds in a region encompassing BA1/2 and S2 (P50.001, r=�0.80 and �0.91, for BA1/2 and S2, respectively; Fig. 3 and Table 5). In addition, mechanical detection thresholds were also negatively correlated with cortical thickness in a slightly more superior BA2 region and the same S2 region (P50.001, r = �0.83 and �0.85, for BA2 and S2, respectively; Fig. 3 and Table 5). However, we did not identify a significant relationship between recovery time and cortical thickness. Therefore, in the post-central gyrus cortical thinning was associated with more severe sensory deficits. However, we did not identify a significant relationship between recovery time and cortical thickness. Again, there was a correspondence between the cortical thinning in areas negatively correlated with vibratory stimuli and the regions showing group fMRI and CTA abnormalities.

White Matter Abnormalities Following Nerve Transection

To assess white matter integrity we utilized a region of interest approach to examine white matter group differences based on a priori hypotheses. Regions of interest were restricted to white matter tracts surrounding and feeding into the contralesional S1 and thalamus. In addition, we also drew regions of interest in white matter adjacent to left and right, anterior and posterior insula. The insula was chosen as it is implicated in somatosensory processing and because we identified reduced grey matter in the right anterior insular with CTA. This region of interest approach revealed that patients had significantly reduced white matter fractional anisotropy values (MANOVA including all six regions of interest) adjacent to the right anterior [F (1, 26) = 4.39, P = 0.046; Fig. 4A] and posterior insula [F (1, 26) = 5.55, P = 0.026; Fig. 4B], but there were no group differences in the white matter adjacent to the left insula (left anterior insula: P = 0.51; left posterior insula: P=0.26), thalamus (P=0.46) or S1 (P=0.46)

Discussion

Here, we have demonstrated for the first time that there is functional plasticity and both grey and white matter structural abnormalities in several cortical areas following upper limb peripheral nerve transection and surgical repair. This plasticity may arise from incomplete peripheral nerve regeneration (peripheral cell death and/or incomplete re-myelination), as nerve conduction measures in these patients demonstrated severe abnormalities. In addition, our data demonstrate that decreased vibrotactile-evoked fMRI responses in the post-central gyrus correspond with grey matter thinning in the patient group. These results suggest that reduced BOLD responses may be facilitated by a reduction in cortical grey matter and/or a decrease in the afferent input to the post-central gyrus. In addition, cortical thickness within these same parts of the post-central gyrus negatively correlated with behavioral measures of somatosensory function. That is, increased somatosensory deficits were correlated with thinner cortex; both of which may be related to afferent input. Taken together, our data suggest that incomplete peripheral nerve regeneration contributes to somatosensory impairments, cortical grey matter atrophy and reduced fMRI activation (see Fig. 5 for a summary of these findings).

It is well known that cortical plasticity following peripheral nerve transection and surgical repair can occur throughout the CNS in non-human primates (Kaas, 1991). This plasticity is thought to be due to the unmasking of previously silent synapses or axonal sprouting into deafferented territory (Wall et al., 1986; Florence and Kaas, 1995). In the primate model, 1 year following nerve transection and surgical repair, the denervated cortex is characterized by incomplete and disorderly representations of the regenerated and adjacent (intact) nerves. This patchy representation is attributed to incomplete peripheral regeneration resulting in a partial recovery of the denervated cortical space (Kaas, 1991). To assess the extent of peripheral regeneration in our patient population we performed sensory and motor nerve conduction studies across the transected area. Our nerve conduction results demonstrate that PNIr patients have significantly decreased amplitude and increased latency in both sensory and motor nerves compared to their own untransected side. Decreased amplitude combined with increased latency is indicative of peripheral fibre loss (i.e. cell death) and/or abnormal or incomplete re-myelination following transection (Kimura, 1984). In addition, it is well established that between 20% and 50% of dorsal root ganglion neurons die following nerve transection (Liss et al., 1996). Thus, afferent cell death and incomplete regeneration can result in decreased afferent input to the cortex, which may account for ongoing sensory deficits and decreased BOLD response in BA2 and S2. Furthermore, this diminished afferent input could also account for the cortical thinning we observed in the same regions of the cortex. Sensory deprivation has been shown to cause trans- neuronal degeneration in several regions of the CNS, including the dorsal horn following sciatic nerve section (Knyihar-Csillik et al., 1989), and may involve second- and third-order neurons (Powell and Erulkar, 1962). Transneuronal degeneration is characterized by cell shrinkage and is thought to be related to decreased, or non-existent, afferent input (Knyihar-Csillik et al., 1989). Thus, cortical grey matter loss (or atrophy) could also be directly related to decreased afferent input.

We also demonstrated increased activation in the post-central gyrus in a region corresponding to BA1/3 (Talairach and Tournoux, 1988). Electrophysiological, anatomical tracing and neuroimaging studies have established that for the majority of cutaneous mechanoreceptive afferents the first cortical destina- tions are BA1 and BA3b. These cytoarchitectonic brain areas each possess a somatotopic body map with small receptive fields. In addition, these areas respond to many features of tactile information, such as texture and roughness, velocity and curvature of stimuli (Bodegard et al., 2001). fMRI studies have demon- strated that activity within the somatosensory cortex is influenced by attention such that fMRI responses to tactile stimuli in S1 are increased when subjects attend to a tactile stimulus, but are atte- nuated when subjects are distracted (Arthurs et al., 2004; Porro et al., 2004). Furthermore, our patients activated a network of brain areas known as the task positive network (DeLuca et al., 2006) more than healthy controls. These brain areas are activated during attention demanding processes (Fox et al., 2005; Seminowicz and Davis, 2007). Together, these findings imply that patients must attend to the stimulus more than controls because of their impaired sensory input. This increased attention may also account for the increased activation in BA1/3b. Of course, the increased activation in BA1/3b may also reflect plasticity that is unrelated to attentional load.

BA2 and S2 both receive projections from BA1/3b and also from distinct parts of the ventroposterior thalamic complex (Pons et al., 1985; Friedman and Murray, 1986). Both of these brain areas have large, often multi-digit (BA2) or bilateral (S2) receptive fields (Pons et al., 1985; Iwamura et al., 2002). Based on ana- tomical projections and neuronal response properties, hierarchical processing of tactile information has been demonstrated from BA1/3b to BA 2 (Kaas et al., 2002). In addition, electrophysiolo- gical studies in macaques (Pons et al., 1987) and magnetoence- phalography data acquired in humans, suggest that serial processing of tactile inputs occurs from S1 to S2 in higher primates (Frot and Mauguiere 1999; Disbrow et al., 2001). Several studies have demonstrated that BA2 is preferentially activated by shape and curvature (Bodegard et al., 2001), while S2 may be involved in tactile learning (Ridley and Ettlinger 1976; Murray and Mishkin, 1984), supporting the notion that these brain areas are involved in higher-order somatosensory processing. Our psychophysical assessment demonstrated that patients were significantly impaired at the detection of simple tactile stimuli, and in the Shape Texture Identification test 1.5 years after surgery (Taylor et al., 2008a). This latter test assesses a patient’s ability to recognize character- istics of an object while actively exploring a shape or texture, requiring the integration of sensory information across regions of the body (Rosen and Lundborg, 1998). Taken together, one inter- pretation of our data is that PNIr patients attend more to the vibrotactile stimulus, leading to increased activation of the task positive network and BA1/3. However, in these patients, our data imply that higher-order processing areas, such as BA2 and S2, did not receive tactile information, which, in turn, may result in cortical thinning and reduced BOLD responses.

The insula is thought to play a role in integrating multimodal information important for sensorimotor, emotional, allostatic/ homeostatic and cognitive functions (Devinsky et al., 1995; Critchley, 2004; Craig, 2008) and has been designated a limbic sensory cortex (Craig, 2008). Several studies have reported insular activation in response to tactile stimulation (Gelnar et al., 1998;

Downar et al., 2002) and anatomical tracing studies in primates have demonstrated that the insula is reciprocally connected to frontal, parietal and temporal lobes (Augustine, 1996). In our patients, the right anterior insula was the only cortical area that demonstrated significant cortical thinning in conjunction with reduced fractional anisotropy values in the adjacent white matter, suggesting that the cortical thinning within this region is associated with a loss of fibres projecting to or from this structure. The right anterior insula has been implicated in interoception as it is situated to integrate homeostatic input from the body with motivational, emotional and social conditions (Craig, 2008). Furthermore, Critchley et al. (2004) reported a correlation between interoceptive abilities and the grey matter volume of the right anterior insula. Given our finding that the patients have decreased grey matter in the right anterior insula, it would be of interest to assess interoceptive capabilities following peripheral nerve injury in a future study.

Taken together, we have demonstrated for the first time that functional and structural alterations are present in the human cerebral cortex 1.5 years after a complete transection of an upper limb peripheral nerve that was microsurgically repaired. In addition, nerve conduction measures indicate incomplete peripheral regeneration in these patients. Furthermore, we show that cortical thickness is related to psychophysical measures of recovery, in that thinner cortex within BA2 and S2 was associated with poorer somatosensory function. These data suggest that the reestablishment of normal functional activation maps is directly associated with the successful regeneration of peripheral afferents.

Keri S. Taylor,1,2 Dimitri J. Anastakis2,3,4 and Karen D. Davis1,2,3

1 Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute, University Health Network, Toronto, Canada M5T258
2 Institute of Medical Science, University of Toronto, Canada
3 Department of Surgery, University of Toronto, Canada
4 Clinical Studies Resource Centre, Toronto Western Research Institute, University Health Network, Toronto, Canada M5T2S8

Correspondence to: Karen D. Davis, Ph.D.,
Division of Brain, Imaging and Behaviour – Systems Neuroscience, Toronto Western Research Institute,
Toronto Western Hospital,
University Health Network,
Room MP14-306, 399 Bathurst Street,
Toronto, Ontario,
Canada M5T 2S8
E-mail: kdavis@uhnres.utoronto.ca

Acknowledgements

The authors thank Mr. Geoff Pope, Dr. Adrian Crawley, Mr. Eugene Hlasny and Mr. Keith Ta for expert technical assistance. The authors would like to thank Dr. Peter Ashby and Mr. Freddy Paiz from the Toronto Western Hospital EMG Clinic for conduct- ing the nerve conduction tests and for providing expert assess- ment of the findings. The authors also thank Drs Dvali, Binhammer, Fialkov and Antonyshyn for collaborating with this project. Dr. Davis is a Canada Research Chair in Brain and Behaviour (CIHR MOP 53304).

Funding

The Physicians’ Services Incorporated and a joint seed grant from the University of Toronto Centre for the Study of Pain/ AstraZeneca.

Supplementary material

Supplementary material is available at Brain online.

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Pyogenic Spinal Infection

• aka Spondylodiscitis and vertebral osteomyelitis overall are relatively infrequent and may present with bimodal distribution: children and adults >50's
• Occasionally considered as two separate entities due to variations in the blood supply of pediatric vs. adult spines
• Risk factors/causes: distant site of infection in the body (25-35%), e.g., oropharynx, urogenital infections, bacterial endocarditis, indwelling catheters, florid skin infections furunculosis/abscess, etc.
• Iatrogenic: operative (e.g., discectomy) interventional or diagnostic/therapeutic procedures
• Penetrating trauma
• Immunocompromised patients
• Diabetics
• Malnourished patients or patients with low protein
• IV drug users
• Chronic disease patients, cancer patients, etc.

Potential Pathological Sequence

Clinical Presentation

• Back pain with or w/o high fever and other "septic" signs. High temperature may only present in 50% of children
• Exacerbation of pre-existing back pain in post-surgical cases
• Neurological complications in advanced cases of vertebral destruction and epidural abscess
• Meningitis, septicemia, etc.
• Labs: Blood tests are unspecific, may or may not indicate elevated ESR/CRP, WBC
• Diagnostic imaging is important but
• If clinical suspicion is strong, prompt I.V. antibiotics are needed to prevent serious complications

Routes of Infection

• Infection routes to the spine are similar to bone in general
• 3-distinct routes: 
• 1) Hematogenous spread as bacteremia (most common)
• 2) Adjacent site of infection (e.g., soft tissue abscess)
• 3)Direct inoculation (e.g., iatrogenic or traumatic)
• M/C organism Staph. Aureus
• Mycobacterium TB (tuberculous spinal osteomyelitis) aka Pott's disease can be presented in cases of re-activated or disseminated pulmonary TB

Mechanisms of Spinal Infection 

• May vary depending on the patients' age
• In children, the IVD receives direct blood supply and can be infected directly spreading to adjacent bone and causing spondylodiscitis

In Adults 

• The disc is avascular
• Pathogens invade adjacent vertebral end-plates via end-arterial supply of the vertebral body that may facilitate infection due to slow, turbulent flow
• Organisms may then quickly gain access to disc substance rich in nutrients (discitis) often w/o significant initially visible destruction to the bone
• Thus, one of the earliest rad. findings of spinal infection or sudden reduction of disc height
• Later end-plate irregularity/sclerosis may develop, subsequently affecting the entire adjacent vertebral bodies

Diagnostic Imaging

• Initially, in most cases of MSK complaints, radiography is the 1st imaging step
• Initially, X-radiography is often unrewarding and may appear unremarkable for 7-10 days or presents with some subtle soft tissue changes (e.g., obscuration of Psoas shadows, etc.)
• Some of the earliest x-ray signs of pyogenic spondylodiscitis: sudden reduction of disc height (above arrow) during initial 7-10 days
• Subsequently (10-20 days) some end-plate irregularity and adjacent sclerosis may be noted
• In more advanced cases, subsequent vertebral destruction and collapse may occur
• N.B. Reliable feature to DDx between spinal infection and metastasis is the preservation of disc height in the latter

Discitis 

• Discitis needs to be DDx from DDD (spondylosis)
• An important DDx between discitis and DDD is lack of osteophytes (spondylophytes) and intradiscal gas (vacuum phenomenon) in DDD.
• Presence the of intradiscal gas (vacuum phenomenon) virtually excludes discitis (except if gas-forming pathogens are involved)
• Note: sudden disc narrowing with no appreciable spondylosis (above the first image) is suspicious for infection (discitis)
• MRI +C is required to evaluate suspected infection
• N.B. 50-60% of pyogenic spondylodiscitis occur in the lumbar region

AP & Lateral Lumbar Radiographs

• Note severe disc narrowing and adjacent vertebral body destruction at L1-L2 in a 68 -y.o.-female with a known Hx of type 2 DM
• Additional imaging modalities should be used to support the Dx
• Final Dx: Pyogenic Spondylodiscitis

Sagittal T1 & T2 MRI

• Weighted MRI slices of a patient who had laminectomy at L4
• MR imaging with gad contrast is the modality of choice for Dx of spinal infection
• Early septic changes affecting the disc and adjacent vertebral end-plates are readily demonstrated as a low signal on T1 and high T2/STIR d/t edema and inflammation
• T1 FS +C gad images show avid enhancement of the lesion due to granulation tissue around the phlegmon. Peripheral enhancement is also characteristic of an abscess.
• Epidural extension/abscess can also be successfully detected my MRI
• N.B. 50% of epidural abscess cases present with neurological signs

STIR & T1 FS +C Gad Sagittal MRI

• Marked septic collection and edema affecting L4-5 disc and vertebral body with some epidural extension and paraspinal soft tissue edema. Avid contrast enhancement is noted surrounding low signal foci within the bone and disc tissue, some gad. Enhancement is observed in posterior paraspinal muscles and dural spaces
• Management: Dx of spondylodiscitis requires prompt I.V antibiotics. If instability and neurological complications develop referral to a Neurosurgeon is required

MRI Unavailable or Contraindicated

• Bone scintigraphy is very sensitive but non-specific for spinal infection but overall is of great value d/t higher sensitivity than x-rays and relatively low cost.
• An area of increased flow with radiopharmaceutical uptake is characteristic but not specific sign of spondylodiscitis
• If neurological symptoms are present and MRI is contraindicated than CT myelography may be used

TB Osteomyelitis aka Pott's Disease

• TB osteomyelitis is increasing d/t HIV and other immunocompromised states. Extrapulmonary TB m/c affects the spine and especially the thoracic spine (60%)
• Radiographic Pathology: TB bacillus infects the vertebral body and often spreads subligamentously. "Cold" paraspinal abscess collection may develop and spreads along fascial planes, e.g., Psoas abscess. Disc spaces are preserved until v. late and skip areas are noted helping to DDx TB from pyogenic infection. Severe vertebral destruction aka Gibbus deformity may develop (>60-degree sometimes) and may become permanent. Neurologic and many regional complications may develop
• Imaging approach: CXR with spinal x-rays 1st step that may be unrewarding but may potentially reveal VB destruction w/o disc narrowing. CT scanning is more superior than x-rays. MRI with gad C is a modality of choice
• Management: isoniazid, rifampin, operative.
• DDx: Fungal/Brucella infection, neoplasms, Charcot spine

Gibbus Deformity & Pott's Disease

Metastatic Bone Disease (aka Mets) or "Secondaries." Are the most common malignant bone neoplasms affecting the spine, aka spinal neoplasms (>70%) and the rest of the skeleton in adults.

• 5-Primaries are m/c involved:
• Breast (16-37%)
• Lung (12-15%)
• Thyroid (4%)
• Renal (3-6%)
• Prostate (9-15%)
• Spine, pelvis, proximal femurs & proximal humeri are m/c affected in that particular order of frequency
• Thoracic & upper Lumbar spine considered the m/c site of spinal Mets

Pathophysiology & Etiology of Metastasis

• Malignant cells a very good at evading immune detection and elimination
• They gain access to circulation expressing Vascular Endothelial Adhesion Molecules (e.g., integrines & selectins)
• Once reaching their target organs, malignant cells stimulate the production of various vasogenic growth factors and by exiting blood vessels invade their target tissues
• Lung, Liver, and Bone are particularly at risk due to the character of their blood supply
• Baston venous plexus-is a network of valveless freely communicating  veins connecting axial skeleton/meninges and proximal femurs/humeri with abdomino-pelvic and thoracic cavities
• The risk of Mets is increased during daily variations in the intra-abdominal and intra-thoracic pressure

• In adults, the axial skeleton is involved in hematopoiesis, and it is particularly vulnerable to metastatic deposits via an abundant network of sinusoids within a spongy bone
• The vast majority of bone Mets will be detected in the axial skeleton

Clinical Presentation

• Back pain often mimicking "mechanical back pain" is the m/c and often misleading symptom
• Chiropractors and other manipulators should be particularly aware of this dangerous pitfall.
• Nocturnal pain or pain unresponsive to NSAID may be reported in more advanced cases
• Advanced cases may also present with a neurological deficit due to pathologic vertebral fractures and spinal cord/nerves compression
• Metastatic hypercalcemia may occasionally develop in severe cases and considered a medical emergency that potentially presents with confusion, muscle weakness, and renal signs
• Imaging plays a significant role in the Dx and management of bone metastasis
• Lab tests are of limited value, but hypercalcemia and alkaline phosphatase (Alk Phos) may be elevated
• In some cases, a bone biopsy may be used to confirm bone Mets

When Bone Mets are Detected, Patients Prognosis is Significantly Worsened

• Median survival:
• Thyroid - 48 - months
• Prostate - 40 - months
• Breast - 24 - months
• Renal Cell - may vary, can be as low as 6 - months
• Lung - 6 - months

Imaging Diagnosis

• Begins with radiography investigating a clinical complaint of back/bone pain
• If radiographs are unrewarding or equivocal, unique imaging modalities are required
• MRI may help to show marrow replacement by Mets foci but limited to specific regions
• Tc99 radionuclide bone scan (scintigraphy) is considered one of the most sensitive and reliable imaging steps in evaluating bone Mets
• Bone scintigraphy is good at detecting both lytic and blastic Mets
• However, very aggressive/vascular osteolytic Mets and Multiple Myeloma often appear "cold" or photopenic on bone scan due to greater stimulation/activation of osteoclasts which "outpace" osteoblasts ability to uptake the radiopharmaceutical
• CT scanning is an excellent modality to show bone destruction, but it is not widely used during bone Mets Dx especially if radiography, bone scintigraphy, and MRI provide adequate information about the process
• CT scanning may be particularly helpful with delineation of pathological fractures

General Radiographic Features of Bone Mets

• Osteolytic (lytic), osteoblastic (blastic) aka sclerotic Mets or misec Mets can be identified radiographically 
• However, it takes between 30-50% of lamella (cortical) bone and 50-75% of trabecular (cancellous) or spongy bone to be destroyed before it can be detected on plain film radiographs
• This can make early radiographic detection of bone Mets very difficult, requiring particular imaging modalities (e.g., MRI)
• Also, bowel gas/fecal matter and numerous soft tissue densities in the abdomino-pelvic and thoracic cavities may pose challenges of bone Mets detection
• Different tumors often manifest with different metastatic appearance, depending on tumor activity and release of cytokines (IL6, IL11), endothelin 1 or other growth factors that will be responsible for either osteolytic, osteoblastic or mixed Mets
• For example: purely lytic bone Mets are noted in Lung, Thyroid, and Renal cell CA (very vascular)
• Breast CA may present with 60% of blastic Mets
• Prostate CA presents with 90% of blastic Mets
• Other blastic Mets may derive from urinary bladder, melanoma and GI adenocarcinomas
• Sclerotic foci may also represent as previously treated primaries
• Very vascular  Mets like Renal cell and Thyroid may present with markedly  lytic and expansile foci often called "blow out Mets."
• Mets found distal to elbows and knees (acro-metastasis) are commonly associated with Lung CA

• PA chest view of a routinely screened patient with a known Hx of Prostatic adenocarcinoma
• Note sclerotic lesion identified in the left posterior Rib 5
• What imaging modality is required next?
• Radionuclide bone scan should be suggested

• Multiple foci of high uptake of the Tc99 radiopharmaceutical
• This is due to Mets and increased osteoblastic activity in the thoracic and lumbar spine, ribs and other sites of the skeleton

• Comparison of purely lytic (a and b) versus blastic (d) and mixed (c) Mets
• What primaries to consider?

• Frog leg view of the hip
• Clinical Dx: Prostatic adenocarcinoma
• Note diffuse blastic Mets in the proximal femur

• Hx: severe shoulder and arm pain unrelieved by rest
• Rad DDx: Mets, Myeloma or less frequently Lymphoma
• This classic DDx is used by the majority of Radiologists when aggressive osteolytic bone lesions are noted
• The patient had a known Hx of Breast CA

• A 51-year-old female with Breast CA
• Large lytic destructive lesion in the distal femoral metaphysis characteristic of aggressive osteolytic Mets

• Sudden onset of severe leg pain and inability to stand in a 53-year-old female with Breast CA
• Dx: Pathological fracture through the distal femoral shaft
• Pathological Mets fractures in the spine and extremities are dreaded by most Oncologists due to higher association with severe complications and poor clinical prognosis

• Radiographic Dx of vertebral Mets should be suspected if a "missing pedicle sign" aka "winking owl sign" is noted
• DDx: pedicle agenesis (above left) shows hypertrophy and sclerosis of a contralateral pedicle d/t increased mechanical stress
• Pedicle Mets are often thought of as the m/c initial site of spinal Mets

Vertebral Body Pathologic Fracture (VERTEBRA PLANA)

• Isolated compression fracture at the T8 segment noted (above arrow)
• The loss of the posterior and anterior height suggest an underlying pathologic condition for which the differential diagnosis includes:
• Multiple myeloma
• Metastatic Carcinoma
• Other malignancy
• Osteoporosis
• Differentiating Pathological Fx of the vertebral body from an osteoporotic insufficiency Fx can be a significant challenge
• Close inspection of the posterior body height is helpful but often not reliable
• In metastasis, the posterior body is collapsed
• In OSP, the posterior body may be maintained appearing more as anteriorly wedge fracture
• MR imaging and/or radionuclide bone scan need to be performed

• A skeletal radiographic survey may be used occasionally for the evaluation of bone Mets especially in well-established cases
• It includes bilateral AP & lateral Thoracic and Lumbar views, AP pelvis, humeri, femurs, and the skull
• Availability of special imaging has supplanted the use of skeletal radiographic survey
• However, in a clinical practice skeletal radiographic study of Multiple Myeloma may still be used primarily if the diagnosis was previously established 

Technetium-99 (99mTc) bone scintigraphy is very sensitive and cost-effective study:

• For the detection/localization of Mets and often an assessment of their biologic activity and response to treatment
• This modality is a well-established part of the workup for known as well as unknown primaries
• It may also help with determination of lesions that will be most accessible and easy to biopsy

• When the burden of Mets is significantly high as shown in the case above
• The radiotracer uptake is being almost entirely taken in by metastatic lesions
• No material is left for the kidneys to excrete
• This is known as a "super scan"

• Sagittal Lumbar and Lower Thoracic MRI. Multiple metastasis are noted on T1 (above right) and T2 (above left)  WI as hypointense foci of marrow replacement of the vertebral bodies in a patient with Hx of Prostate CA
• MR imaging protocol with T1, T2, and T1+C gad can be used in many cases if x-radiography is unrewarding or questionable
•  MRI can reveal bone marrow changes due to bone marrow replacement by Mets and surrounding edema
• Typically blastic Mets appear as abnormally decreased signal intensity (hypointense) lesions on T1 and T2 pulse sequences
• Purely lytic Mets often appear as hypo-intense on T1 and hype-intense on T2
• Increased gadolinium uptake may also be evident on T1+C fat suppressed sequence d/t increased vascularity of malignant foci especially in very aggressive vascular neoplasms

• Sagittal Lumbar and Lower Thoracic MRI. Multiple metastasis are noted on T1 (above right) and T2 (above left)  WI as hypointense foci of marrow replacement of the vertebral bodies in a patient with Hx of Prostate CA
• MR imaging protocol with T1, T2, and T1+C gad can be used in many cases if x-radiography is unrewarding or questionable
•  MRI can reveal bone marrow changes due to bone marrow replacement by Mets and surrounding edema
• Typically blastic Mets appear as abnormally decreased signal intensity (hypointense) lesions on T1 and T2 pulse sequences
• Purely lytic Mets often appear as hypo-intense on T1 and hype-intense on T2
• Increased gadolinium uptake may also be evident on T1+C fat suppressed sequence d/t increased vascularity of malignant foci especially in very aggressive vascular neoplasms

Spinal Neoplasms

Degenerative Arthritis

• Spinal Arthritis:
• Spondylosis aka Degenerative disease of the spine represents an evolution of changes affecting most mobile spinal segments beginning with:
• Intervertebral disc (IVD) dehydration (desiccation) and degeneration aka Degenerative Disc Disease (DDD) with an abnormal increase in mechanical stress and degeneration of posterior elements affecting 4-mobile synovial articulations ( true osteoarthritis)
• 2-Facets in the L/S & 2-Facets & 2-Uncovertebral joints in the C/S
• Imaging plays a significant role in the diagnosis, grading, and evaluation of neurological complications (e.g., spondylotic myelopathy/radiculopathy)
• X-radiography with AP, Lateral & Oblique spinal views provides Dx and classification of Spondylosis
• MR imaging may help to evaluate the degree of neurological changes associated with degenerative spinal canal and neural foraminal stenosis

• Spinal motion segment:
• 2-adjacent vertebrae
• IVD (fibrocartilage)
• 2-facets (synovial)
• Pathology: loss of disc height increases mechanical stress on mobile elements
• Ligamentous laxity/local instability
• Spinal osteophytes aka spondylophytes & bony facet/uncinate proliferation
• Disc herniation and often disc-osteophyte complex
• Ligamentum flavum "hypertrophy" or thickening due to buckling
• Loss of normal lordosis with or w/o reversal or kyphosis
• Vertebral canal & neural foraminal stenosis

Neutral lateral cervical radiograph: note mild to moderate disc narrowing and spondylophyte formation at C5-6 & C6-C7 (most common levels affected by cervical spondylosis). Straightening or flattening with mild reversal of cervical lordosis. Some mild facet proliferation is noted at the above levels

• On radiographs: evaluate for disc height (mild, moderate or severe) loss
• End-plate sclerosis & spondylophytes; mild, moderate or severe
• Facet and uncinate irregularity, hypertrophy/degeneration; mild, moderate or severe
• Note degenerative instability aka degenerative spondylolisthesis/retrolisthesis
• Normal or lost lordosis vs. degenerative kyphosis
• Key Dx: correlate with a clinical presentation: neck/back pain with or w/o neurological disturbance ( myelopathy vs. radiculopathy or both)

• Uncinate processes undergo degeneration/proliferation resulting in uncovertebral arthrosis
• Early findings present with mild bone proliferation along the cortical margin (white and black arrows) if compared to normal uncinate (orange arrow)
• Later, more extensive bone proliferation extending into and narrowing vertebral canal and neural osseous foramina (IVF's) may be noted. The latter may contribute to spinal/IVF stenosis and potential neurological changes
• Posterior oblique views may help further

• AP lower cervical (a) and posterior oblique (b) views
• Note mild uncinated process proliferation with neural foraminal narrowing (arrows)
• Typically if less than a third of IVF becomes narrowed, patients may present w/o significant neurological signs

• Lumbar spondylosis is evaluated with AP and lateral views with additional AP L5-S1 spot view to examine lumbosacral junction
• Typical features include disc height loss/degeneration
• Intra-discal gas (vacuum) phenomenon (blue arrow) along with spondylophytes
• Degenerative spondylolisthesis and/or retrolisthesis (green arrow) may follow disc and facet degeneration and can be graded by the Meyerding classification
• In most cases, degenerative spondylolisthesis rarely progresses beyond Grade 2
• Lumbar facet degeneration seen as bone proliferation/sclerosis and IVF narrowing

• MR imaging w/o gad C is an effective modality to evaluate clinical signs of spondylosis & associated neurological complications with pre-surgical evaluation
• Case: 50-y.o Fe with neck pain. Case b-45-y.o.M (top a b images). MRI reveals: loss of disc hydration or desiccation, spondylophytes and disc herniation w/o neurological changes
• (Bottom images) Left: preoperative and right postoperative MRI slices of the patient presented with clinical signs of cervical spondylotic myelopathy. Note disc herniation, ligam flavum hypertrophy and canal stenosis (left)

• Sagittal MRI slice of lumbar DDD manifested with disc desiccation and posterior herniation effacing thecal sac
• Correlating sagittal and axial slices will be more informative to evaluate canal stenosis and potential degree of neurological involvement (above-bottom images)

• Use the following resources to learn more on MRI evaluation and diagnosis of Degenerative Disc Disease:
• https://radiopaedia.org/articles/intervertebral-disc-disease-nomenclature
• https://ac.els-cdn.com/S1529943014004094/1-s2.0-S1529943014004094-main.pdf?_tid=bab686bc-cf70-4479-a243-b6d2b342461c&acdnat=1535573367_98364d2d06b7c967d3e859e785eb6f13

Diffuse Idiopathic Skeletal Hyperostosis (DISH) aka Forestier disease

• Flowing degenerative ossification of ALL
• M/c Thoracic spine. 2nd m/c-cervical spine
• Dx by imaging only. X-radiography is sufficient
• CT w/o contrast helps with Dx of Fx
• Men>women. Pts>60-y.o. Extensive DISH shows 49% association with type 2DM
• Complications: Chalk (carrot) stick Fx. Unstable 3-column Fx requiring surgical fusion

• Sagittal reconstructed CT scan slice in bone window
• Chalk stick Fx at C5-C6 in the patient with DISH and OPLL

Spinal Arthritis

Imaging Diagnosis Management:

• Cervical spinal trauma & radiographic variants simulating disease
• Cervical spine
• Arthritis
• Neoplasms
• Infection
• Post-Surgical cervical spine

• Cranio-cervical and upper cervical stability is dependent on transverse, superior and inferior bands of the C1-C2 ligament, alar ligaments, along with a few other ligaments

Cervical Trauma

• The C/S is vulnerable to injury. Why?
• Stability has been sacrificed for greater mobility
• Cervical vertebrae are small and interrupted by multiple foraminae
• The head is disproportionately heavy and acts as an abnormal lever especially when forces act against a rigid torso
• Additionally, C/S is prone to degeneration which makes it more vulnerable to trauma
• In young children, ligaments are more luxed vs. disproportionately large head size
• In children, the fulcrum of movement is at C2/3 thus making injuries more common in the upper C/S and craniocervical junction. In children, S.C.I.W.O.R.A. may occur when no evidence of fracture present
• In adults, the fulcrum of movement is at C5/6 thus making lower C/S more vulnerable to trauma especially during extremes of flexion
• Cervical Trauma categorized according to mechanisms of injury (Harris & Mirvis classification)

Hyperflexion Injury: Stable vs. Unstable

• Flexion teardrop Fx (most severe fracture, unstable)
• Bilateral facet dislocation (severe injury w/o fracture, unstable)
• Anterior subluxation (potentially unstable) can be very subtle injury
• Clay Shoveller Fx (lower C/S SP avulsion, stable)
• Simple wedge compression (most benign Fx, stable)
• Hyperflexion-rotation with unilateral facet dislocation
• Obtain a thorough history
• Perform physical exam including a neurological exam
• Consider NEXUS criteria (National Emergency X-radiography Utilization Study)

Imaging Techniques:

• Begins with x-radiography especially in cases with no significant neurological compromise
• Clear neutral lateral view first
• If x-radiography is unrewarding but high probability of severe trauma and neurological deficit present, CT scanning w/o contrast is required
• Consider CT scanning in patients with pre-existing changes: advance spondylosis, DISH, AS, RA, post-surgical spine, congenital abnormalities (Klippel-Feil syndrome, etc.)

Vertical compression:

• Jefferson aka burst Atlas Fx (unstable especially if the Transverse ligament is torn, cord paralysis in 20-30% only)
• Why? Due to fragments dissociation and canal widening
• Burst Fx of the Thoracic or Lumbar spine (unstable, cord paralysis may occur)

How to Assess Spinal Radiographs in Trauma Cases:

• Construct 5-lines on the lateral view
• Note if facets are well-aligned and symmetrical
• Ensure symmetry of the disc height
• Note any widening or fanning of the inter-spinous distance
• Carefully examine prevertebral soft tissues
• Evaluate atlanto-dental interval (ADI)

• In cases of trauma, evaluate and clear neutral lateral first
• Do not perform flexed and extended views in acute cases before x-rays or CT scanning exclude significant instability
• Pay extra attention to prevertebral soft tissues
• If thicker than normal limits, consider severe post-traumatic bleed
• Subtle asymmetry and widening of posterior disc height and facets with inter-spinous fanning may be a key feature of significant tearing of posterior ligaments

Hyperflexion Injuries (M/C Mechanism)

• More frequent in sub-axial C/S C-3-C7)
• Unstable injuries:
• Flexion teardrop fracture (M/C C5 & C6) v. unstable
• Key rad features:
• Large "teardrop" triangular anterior body fragment
• Fanning of the SPs, posterior disc and facet widening indicating tearing of major spinal ligaments and instability
• A posterior shift of the vertebral body fracture suggests direct anterior cord/vessels compression
• Bulging prevertebral soft tissue >20-mm at C6-7
• 80% of cases may be paralyzed on the spot or develop significant paralysis soon after

Acute Neck Trauma. What are the vital radiographic features? What is the diagnosis?

• CT scanning w/o contrasts with sagittal reconstruction. Note C7 Flexion teardrop Fx.
• CT may help with further delineation and preoperative planning
• May follow with MR imaging and evaluation of the neurological injury

• Fluid sensitive (T2) sagittal MRI slice of Flexion teardrop fracture at C4 and possibly C5
• Note high signal intensity lesion in the cord and surrounding ligaments indicating cord edema and ischemia
• Management: neurosurgical with spinal fusion
• Complications:
• Quadriplegia/paraplegia
• Respiratory complications
• Disability, changes in the quality of life
• Decreased life expectancy

• Bilateral facet dislocation (unstable)
• Mechanism: Flexion-distraction injury
• Key radiography: anteriorly displaced body 50% or more
• Facets override and locked (can be perched left image)
• Major tearing of ligaments
• Chances of severe cord compression and paralysis
• Patients with ligaments laxity and degenerative changes are at higher risk
• Initial x-radiography is the first step

CT scanning w/o Contrast is Crucial:

• Further delineation of this injury
• Facet fractures, pedicle fracture
• Management planning

Sagittal fluid sensitive MRI of bilateral C5 facet dislocation, sizeable ischemic cord injury, and posterior soft tissue injuries

• Management:
• X-radiography, then CT scanning then immediate closed reduction (esp. if the patient is conscious)
• Followed in some more complicated cases by MRI and then surgical care
• If the patient is awake and neurologically stable, CT and closed reduction are adequate
• Complicated cases and failed closed reduction may require surgical stabilization
• Complications: spinal cord injury and paralysis
• Delayed ligamentous laxity and instability

• Unilateral facet dislocation (flexion-rotation injury) less severe than bilateral dislocation
• Most commonly missed unstable cervical injury on x-radiography
• Key rad features: body anteriorly translated 25% facets appear misaligned and blurred, SPs rotated on frontal views
• Clinically may be presented as one-sided radiculopathy esp. C6 or C7
• CT scanning is required to evaluate further facet/pedicle fractures
• Pre-reduction evaluation and care planning
• Management: closed reduction esp. in a conscious patient
• Complications: acute disc herniation/retropulsion, ligamentous laxity, neurological injury

• https://emedicine.medscape.com/article/824380-overview
• https://emedicine.medscape.com/article/248236-overview#a9
• https://emedicine.medscape.com/article/397896-overview#a3
• https://www.aafp.org/afp/1999/p331.html