Author: virtualmedstudent

An Overview of the Sciatic Nerve

virtualmedstudent

The sciatic nerve is a collection of nerve fibers that exit the spinal column between the 4th lumbar and 3rd sacral levels (L4-S3).

In the upper leg, the sciatic nerve gives off branches to the hamstring muscles. These muscles, which include the semimembranous, semitendinous, biceps femoris and part of the adductor magnus, are powerful flexors of the knee joint.

After sending off branches to the hamstrings, the sciatic nerve hits the back of the knee. At the popliteal fossa the sciatic splits into two distinct nerves: the common peroneal nerve and the tibial nerve.

The first nerve, the common peroneal (aka: common fibular), wraps around the outside of the knee and over the head of the fibula. It then branches into two separate nerves: the superficial peroneal and deep peroneal nerves.

The superficial peroneal nerve innervates two muscles: peroneus longus and brevis (aka: fibularis longus and brevis). These muscles allow you to evert (ie: allow you to lift your "pinky" toe higher than your "big" toe) and plantarflex (ie: help you step on the gas pedal) the foot. This nerve also provides the sensation to the outside half (ie: lateral half) of the lower leg, as well as the top of the foot.

The deep peroneal nerve innervates three muscles in the leg: tibialis anterior, extensor digitorum longus, and extensor hallucis longus. Tibialis anterior allows you to dorsiflex (ie: lift your foot off the ground) and invert (ie: bring your "big" toe higher than your "pinky" toe) your foot. Extensor digitorum longus helps you extend your toes (ie: the opposite of curling them), as well as evert, and dorsiflex your foot. The third muscle, extensor hallucis longus allows you to extend your big toe.

The deep peroneal nerve also innervates two muscles in the foot: extensor digitorum brevis (also helps to extend the toes) and extensor hallucis brevis (also helps to extend the big toe).

Peroneal Nerve and its Branches
Branch Muscles
Superficial peroneal – Peroneus longus
– Peroneus brevis
Deep peroneal
(leg branches) 		– Tibialis anterior
– Extensor digitorum longus
– Extensor hallucis longus
Deep peroneal
(foot branches)		 – Extensor digitorum brevis
– Extensor hallucis brevis

The other branch of the sciatic nerve, the tibial nerve, dives deep into the lower part of the leg where it acts on muscles in the calf and foot. In the calf it innervates the gastrocnemius (commonly called the "calf" muscle), soleus, popliteus, plantaris, flexor digitorum longus, flexor hallucis longus, and tibialis posterior. The gastrocnemius, soleus, and tibialis posterior are important plantarflexors of the foot (ie: allow you to "step on the gas pedal"). Flexor digitorum longus and flexor hallucis help flex (ie: curl) the toes.

The tibial nerve also sends branches into the foot. It further branches into the medial plantar and lateral plantar nerves, which innervate numerous muscles (see table below) in the foot itself.

The tibial nerve branches in the foot, namely the medial plantar and lateral plantar nerves also provide sensation to the sole of the foot.

Tibial Nerve and its Branches
Branch Muscles
Tibial nerve (leg branches) – Gastrocnemius
– Soleus
– Popliteus
– Plantaris
– Flexor digitorum longus
– Flexor hallucis longus
– Tibialis posterior

Tibial nerve (foot branches) -> medial plantar nerve

– Abductor hallucis
– Flexor digitorum brevis
– First lumbrical
Tibial nerve (foot branches) ->
lateral plantar nerve 		– Flexor digiti minimi
– Adductor hallucis
– Interossei
– 2nd, 3rd, 4th lumbricals
– Abductor digiti minimi

Importance in Disease

The most well known problem of the sciatic nerve is a condition termed "sciatica". Sciatica is not a disease or disorder in itself, but rather a symptom of some underlying spine or nerve pathology. It is most often due to compression of one or more of the nerve roots that contribute axons to the sciatic nerve (L4-S3).

Compression of the nerve roots can be caused by many different pathologies, of which the most common is a herniated disc. Other causes include spinal stenosis and spondylolisthesis. Rarely, the nerve itself is compressed at some point as it travels down the leg.

A common symptom of sciatica is a severe and sharp pain that starts in the lower back and shoots down the buttock and back of the leg. If the involved nerve roots are severely compressed, weakness may also occur. This can cause a "foot drop" (ie: an inability to lift your foot off the ground).

The sciatic nerve may also get compressed as it passes through the piriformis muscle in the pelvis. When this occurs weakness of the hamstrings, lower leg, and foot muscles occurs; in addition, sensation of the outside of the lower leg, the calf, and the sole of the foot may also be affected.

Overview

The sciatic nerve is really two nerves that split at the level of the knee. The two main branches are the common peroneal (aka: common fibular) and tibial nerves, each of which branch again to innervate different muscles in the lower leg and foot. The most common pathologic problem with the sciatic nerve is a constellation of symptoms termed "sciatica". Sciatica is caused, most commonly, by compression of the nerve roots (L4-S3) in the spine that give rise to the sciatic nerve.

More Anatomy You Should Know…

References and Resources

The Median Nerve: Anatomy, Function, and Clinical Relevance

virtualmedstudent

Radial Nerve Course
In order to appreciate the median nerve, we have to first understand the brachial plexus. The brachial plexus can be thought of as a massive system of highway intersections, in which numerous highways come together and then split apart.

The "highways" merging into the brachial plexus are the 5th, 6th, 7th, and 8th cervical nerve roots, as well as the 1st thoracic nerve root. These nerve roots mix together to form trunks, divisions, cords, and finally branches. The median nerve is one of the final branches of the brachial plexus. It is composed of fibers from the 6th, 7th and 8th cervical nerve roots, as well as the 1st thoracic nerve root.

After branching from the brachial plexus, the median nerve courses along the front aspect of the humerus in the upper arm. At the elbow it branches to supply the pronator teres, flexor carpi radialis, palmaris longus, and flexor digitorum superficialis muscles.

In the forearm the nerve divides into a branch called the anterior interosseous nerve, which supplies the flexor pollicis longus, flexor digitorum profundus (more specifically the lateral head, the medial being supplied by the ulnar nerve), and the pronator quadratus muscles.

The other forearm branch travels into the hand where it supplies the abductor pollicis brevis (abductor pollicis longus is supplied by the radial nerve), flexor pollicis brevis, opponens pollicis, and the first and second lumbrical muscles. This branch also supplies the skin on the palmar side of the hand including the thumb, index, middle, and lateral half of the ring finger (see picture below).

For the most part the median nerve and its branches are involved in muscles that allow joints to flex, especially at the wrist and fingers.

Muscles Innervated by the Median Nerve and its Branches
Muscle Action of Muscle
Pronator teres Pronates the hand (ie: facing the palm towards the floor as if you were patting a dog)
Flexor carpi radialis Flexion of the wrist
Flexor digitorum superficialis Flexion of the proximal interphalangeal joints primarily (ie: flexion of the second knuckles of the fingers)
Palmaris longus Variable, frequently not even present in some people
Flexor digitorum profundus (lateral half of the muscle) Helps flex all the fingers joints (ie: as if you were squeezing something or making a fist)
Flexor pollicis longus Helps flex the thumb
Pronator quadratus Helps pronate the hand (as if you were "patting" a dog)
Opponens pollicis Helps oppose the thumb (ie: bringing the thumb towards the little finger)
Lumbricals (1st and 2nd) Help flex the metacarpophalangeal joints and extend the interphalangeal joints of the index and middle fingers
Abductor pollicis brevis Helps abduct the thumb (ie: moving your thumb further from the palm)
Flexor pollicis brevis Helps flex the thumb

Importance in Disease

Median Nerve Sensory Distribution in Hand
Damage to the median nerve occurs at one of three places along its course. It may be compressed by the two heads of the pronator teres muscle near the elbow, or at the wrist in the carpal tunnel. Additionally, the anterior interosseous nerve may become compressed in the forearm.

Patients with compression of the nerve by the pronator teres muscle have an inability to flex the index or middle fingers. This is due to dysfunction in the flexor digitorum profundus and first and second lumbricals. The ability to flex or oppose the thumb is also affected because of flexor pollicis longus and brevis dysfunction, as well as opponens pollicis muscle dysfunction. Abduction of the thumb is moderately affected because abductor pollicis brevis is affected; however, abductor pollicis longus is innervated by the radial nerve so some thumb abduction may be possible. The muscles affected above can cause the "hand of Benediction" sign when the patient is asked to make a fist. Finally, there is decreased sensation in the distribution of the median nerve in the hand (see image to right).

Compression of the anterior interosseous nerve can occur in the forearm. The flexor digitorum profundus and flexor pollicis longus muscles are affected, which causes a decreased ability to flex the thumb, index, and middle fingers. This causes an abnormal "pinch attitude" when the patient is asked to make an "OK" sign with their index finger and thumb. Sensation is normal.

The nerve can also get trapped in the carpal tunnel near the wrist. Patients typically have weakness in the abductor pollicis brevis, flexor pollicis brevis, opponens pollicis, and the first two lumbricals. This causes decreased thumb, index, and middle finger function. In addition, sensation is affected. Patients with carpal tunnel syndrome typically have pain, numbness, and tingling in their affected hand, which is worst at night. This is in contrast to pronator teres compression in which the sensation changes are not exacerbated at night.

Overview

The median nerve is one of the terminal branches of the brachial plexus. It sends branches to the main wrist and finger flexors, as well as many of the muscles that control thumb function. It provides sensation to most of the palmar side of the hand. It gives rise to three syndromes: pronator teres syndrome, anterior interosseous syndrome, and carpal tunnel syndrome depending on where along its course the nerve is affected.

Related Anatomy You Should Know About…

References and Resources

Radial Nerve and the Saturday Night Palsy

virtualmedstudent

Radial Nerve Course
In order to appreciate the radial nerve, we have to first understand the brachial plexus. The brachial plexus can be thought of as a massive highway intersection, in which numerous highways come together and then split apart again.

The "highways" merging into the brachial plexus are the 5th, 6th, 7th, and 8th cervical nerve roots, as well as the 1st thoracic nerve root. These nerve "highways" tangle together to form trunks, divisions, cords, and then branches. The radial nerve is one of the branches of the brachial plexus; it gets its input from the 5th, 6th, 7th and 8th cervical nerve roots.

The radial nerve courses along the humerus in the upper arm. It wraps around the humerus in a spot called the spiral groove. Just before wrapping around the humerus, it sends a branch that innervates the triceps muscle (long, medial, and lateral heads) in the upper arm.

After wrapping around the spiral groove, it sends additional branches to the brachioradialis, extensor carpi radialis longus, and extensor carpi radialis brevis muscles.

The first major branch in the forearm is known as the superficial radial nerve. This nerve courses along the medial/ulnar aspect of the forearm (ie: the ulnar or medial side of the forearm is closest to your body when your palms are facing forward) and heads straight for the hand. It relays sensory information from the lateral portion of the back of the hand.

The second major branch at the elbow can be thought of as the deep radial nerve, but it is formally known as the posterior interosseous nerve.

The posterior interosseus nerve sends branches to eight muscles in the forearm. They include the supinator (through which the nerve travels via a fibrous tunnel known as the arcade of Frohse), extensor digiti minimi, extensor carpi ulnaris, extensor digitorum, abductor pollicis longus, extensor pollicis longus, extensor pollicis brevis, and extensor indicis.

Muscles Innervated by the Radial Nerve and Its Branches
Muscle Action of Muscle
Triceps brachii – Extension of the forearm away from upper arm
Brachioradialis – Helps flex the forearm closer to the upper arm
– Helps supinate (ie: palm towards the sky)
– Helps pronate (ie: palm towards the floor)
Extensor carpi radialis
(longus and brevis)		 – Helps extend the wrist
– Abducts the hand (ie: hand moves away from
the body when the palms are facing forward)
Extensor digiti minimi – Helps extend the little finger (5th digit)
Extensor carpi ulnaris – Helps extend the wrist
– Adducts the hand (ie: hand moves towards
the body when the palms are facing forward)
Supinator – Allows palms to face up towards the sky
Extensor digitorum – Helps with extension of the fingers
(specifically at the metacarpophalngeal joint)
Abductor pollicis longus – Helps abduct the thumb
Extensor pollicis
(longus and brevis)		 – Help extend the thumb
Extensor indicis – Helps extend the index finger

Generally speaking, the radial nerve and its branches are involved in muscles that allow joints to extend (ie: widen or separate away from one another).

Importance in Disease

Damage to the radial nerve may take the form of compression or sheering injuries, typically after traumatic events.

The most common site of injury is at the spiral groove of the humerus. The nerve may be damaged if someone breaks their humerus, or if someone leans the back of their arm on something for an extended period of time (ie: a "Saturday night palsy" is the informal term given to a drunk who falls asleep with their arms draped over a chair… they end up waking up with a radial nerve palsy!).

Injury to the nerve at the spiral groove causes a wrist drop, in which the affected person cannot extend their wrist. The triceps are not affected because nerve branches to this muscle are proximal to the spiral groove. In addition, patients also complain of decreased sensation on the back of the hand (see image to right).

Radial Nerve Sensory Distribution in Hand
Additionally, the posterior interosseous branch of the radial nerve may get compressed as it passes through the supinator muscle in the forearm. This is referred to as posterior interosseous nerve syndrome.

The compression occurs at a fibrous portion of the supinator muscle known as the "arcade of Frohse", which causes an inability to extend the fingers at the metacarpophalangeal joints; this is due to dysfunction of the extensor digitorum muscle (extension at the interphalangeal – both distal and proximal – joints is controlled by the lumbricals and interossei muscles which are innervated by the median and ulnar nerves).

In posterior interosseous nerve syndrome it is still possible to extend the wrist because the branches of the nerve to the extensor carpi radialis muscle are unaffected (ie: they branch before the arcade). However, when the wrist is extended it deviates towards the radial side of the forearm because of the unopposed action of the extensor carpi radialis muscles (in other words, the extensor carpi ulnaris is affected and cannot keep the wrist extension neutral).

Sensation is entirely normal when the posterior interosseous nerve gets compressed because it contains no sensory fibers.

Overview

The radial nerve is a terminal branch of the brachial plexus. It sends branches to most of the extensor muscles of the arm and forearm. It also provides sensation to the back side of the hand. If injured it causes either a radial nerve palsy, or posterior interosseous syndrome, in which the affected patient has an inability to extend various joints at the wrist and/or fingers.

Related Anatomy You Should Know About…

References and Resources

  • Ducic I, Felder JM 3rd, Quadri HS. Common nerve decompressions of the upper extremity: reliable exposure using shorter incisions. Ann Plast Surg. 2012 Jun;68(6):606-9
  • Colbert SH, Mackinnon SE. Nerve compressions in the upper extremity. Mo Med. 2008 Nov-Dec;105(6):527-35.
  • Reddy MP. Peripheral nerve entrapment syndromes. Am Fam Physician. 1983 Nov;28(5):133-43.
  • Calfee RP, Wilson JM, Wong AH. Variations in the anatomic relations of the posterior interosseous nerve associated with proximal forearm trauma. J Bone Joint Surg Am. 2011 Jan 5;93(1):81-90.
  • Arle JE, Zager EL. Surgical treatment of common entrapment neuropathies in the upper limbs. Muscle Nerve. 2000 Aug;23(8):1160-74.

Burrill B. Crohn and His Disease: GI Inflammation

virtualmedstudent

Crohn’s disease is one of the inflammatory bowel diseases. Its pathology is related to transmural (ie: full wall thickness) inflammation of the bowel wall. Why this inflammation occurs is not particularly well understood.

Genetics appears to play an important role. Specific human leukocyte antigen genes are associated with Crohn’s (DR1/DQ5). In addition, there is a gene known as IBD1 that increases the risk of Crohn’s disease. The IBD1 gene encodes a protein called NOD2. This protein normally helps people “contain” bacteria in the gut. In some patients with Crohn’s disease the protein is mutated and does not function properly.

The immune system also plays an important role. For reasons that are actively being researched patients with inflammatory bowel disease may attack bacteria in the intestine that would otherwise be left alone. This leads to inflammation of the gut wall. Why dysregulation of the immune system occurs is not well understood, but many different types of immune cells are involved including T-cells, neutrophils, and macrophages.

The inflammation in Crohn’s disease can affect almost any location in the gastrointestinal tract from the mouth to the colon. The terminal ileum and proximal colon are the most common sites affected. Roughly 40% of cases involve the small bowel only. Pathological specimens resected from patients with the disease show noncaseating granulomas, aggregates of lymphocytes (ie: a type of white blood cell) in the bowel wall, and extension of fat along the serosal surface.

Signs and Symptoms

Symptoms usually start between the ages of 15 and 40, with a second smaller peak starting between 50 and 80. Men and women are affected equally.

Diarrhea, abdominal pain, and weight loss that are chronic, or occur repeatedly are concerning for Crohn’s. Blood in the stool is not always seen, but may be present. Since any portion of the gastrointestinal tract can be involved, some patients have oral manifestations such as aphthous ulcers (“canker sores”).

Complications can occur and include bowel wall perforation, abscess formation, and strictures (ie: narrowing) of the bowel’s diameter resulting in obstruction. Fistulas, which are abnormal connections between two unrelated organs/body parts can occur between the bowel and the skin (enterocutaneous), bowel and bladder (enterovesicular), bowel and vagina (enterovaginal), and between adjacent bowel segments (enteroenteric).

Non-intestinal manifestations are also common. They include an arthritis that migrates around the body and involves multiple joints. Uveitis is inflammation of the uvea of the eye, which can lead to a painful eye and vision problems. Ankylosing spondylitis and sacroiliitis are inflammatory conditions of the axial skeleton that can co-exist with Crohn’s. Erythema nodosum, which is inflammation of the fat cells under the skin commonly occurs around the shins in patient’s with Crohn’s. Finally, primary sclerosing cholangitis (PSC), which is inflammation of the bile ducts, both inside and outside the liver, can also occur (PSC is more strongly associated with ulcerative colitis).

Patient’s with long standing Crohn’s disease are also at risk of developing colon cancer, although the risk is less than that seen in ulcerative colitis.

Diagnosis

The diagnosis is based on the history provided by the patient and imaging studies. Imaging studies can be x-rays taken after contrast is given (barium). The x-rays may show a “string sign”. The string sign is a result of nodular outpouchings of the bowel wall (secondary to inflammation), alternating with normal areas.

CT and MRI scans of the abdomen with contrast can show increased thickness of the bowel wall; they can also show abscess and fistulae formation, which are complications of the disease.

The "gold standard" for diagnosis is colonoscopy with biopsy of affected tissue. Skip lesions, in which areas of inflammation alternate with normal bowel, are highly suggestive of Crohn’s disease. The bowel wall will often appear “cobblestoned” and aphthous ulcers may also be present along the mucosal surface.

Treatment

Active Crohn’s disease is usually treated with one or more medications depending on the severity. Severe flairs of the disease are treated with steroids like prednisone.

Mild to moderate disease is often treated with one of the 5-aminosalicylic acid (5-ASA) derivatives. Sulfasalazine and mesalamine are two such derivatives. Unfortunately, 5-ASA medications do not appear to prevent relapses.

Some patients will not respond to prednisone or 5-ASA medications. For disease that does not respond to the above medications there are other options such as azathioprine and methotrexate.

Finally a class of medications known as “biologics” can be used. These medications dampen the immume response and therefore decrease the inflammation that occurs in autoimmune diseases. These include the anti-tumor necrosis factor medications known as infliximab and adalimumab. Vedolizumab (Entyvio®) blocks integrins on the surface of immune cells from binding to cells in the GI system. Ustekinumab (Stelara®) works on a molecule known as an interleukin, which is involved in inflammation. And last, but not least, risankizumab (Skyrizi®) also blocks a specific interleukin (number 23 to be exact), which decreases inflammation.

Overview

Crohn’s disease is characterized by inflammation of the entire bowel wall. It manifests with both gastrointestinal and extra-intestinal symptoms. It is diagnosed by history and imaging studies. Treatment is with immune dampening therapies like prednisone, 5-ASA derivatives, azathioprine, 6-mercaptopurine, methotrexate, and tumor necrosis factor inhibitors.

Other Stuff You May Want to Learn About

References and Resources

  • Gura Y, Bonen DK, Inohara N, et al. Frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 2001 May 31;411(6837):603-6.
  • Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Tenth Edition. Philadelphia: Elsevier Saunders, 2004.
  • Akobeng AK, Gardener ES. Oral 5-aminosalicylic acid for maintenance of medically-induced remission in Crohn’s Disease. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD003715.

The Best Medical Books for Your Library

virtualmedstudent

When I was in medical school one of my professors told me that as medical students we learn more, and forget more, in four years than most people learn in a lifetime! I would say he was absolutely correct! The vast amounts of knowledge in the medical sciences makes picking the proper books to study from even more important. In general I recommend avoiding books that are likely to change frequently over time and stick with the ones that you’ll go back to repeatedly. Below are a few books I found particularly useful during my years as a student. They are organized by year with a brief explanation of why I chose each book.

Years 1 and 2

For most medical schools most of year one and year two are going to be about developing an understanding of normal anatomy and physiology and then what happens when things go awry!

                

  • Robbins & Cotran Pathologic Basis of Disease – Although expensive, this book has every single fact about pathology that you’ll need to know. It covers every organ system and disease in excruciating detail. It may be a bit too dense for everyday reading, but it is a great resource when you want to dig deep on a particular topic.
  • Pathophysiology of Heart Disease: An Introduction to Cardiovascular Medicine. This books was the result of a collaborative effort by Harvard faculty and medical students. It is extremely well written and easy to understand. I referenced this book numerous times not only during 1st and 2nd years but into the clinical years as well. If you want to know how old I am, I had the first edition and I think it is now in its 7th edition (geesh!).
  • Clinical Microbiology Made Ridiculously Simple. Great for learning the basics of microbiology. It has all the important bugs and anti-microbials that you’ll need to know. Written using funny language and pictures that helps the info stick. If you need more than this for medical school then you’re probably headed towards a career in infectious disease.
  • First Aid for the USMLE Step 1. The "bible" for USMLE step 1 studying… Need I say more? But in all honesty it is a nice book, but you have to “work” with it. It could be organized better, but if you really sit down with it and fact check its information you will rock step 1.
  • Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Again another pricey book, but one that will become part of your medical library throughout your training. It has everything you need to know about pharmacology and medications.
  • Duus’ Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. I have the OG version from 2005, but it has been updated a few times since then. Excellent illustration of neurology and neuroanatomy. This is really a basic sciences course book, but I like it because it has a very heavy clinical bent to it, which prepares you well for the clerkships.
  • Renal and Electrolyte Disorders. Great book, highly recommended for understanding those darn pesky kidneys! And it’s relatively cheap so that’s a bonus!
  • Moore’s Clinically Oriented Anatomy. This book is essential… Especially for all the future surgeons in the room. I used this book along with the atlas (next on the list) to get a good grip on anatomy.
  • Color Atlas of Anatomy: A Photographic Study of the Human Body. I tried using Netter’s (for fear of having my head ripped off is a decent atlas), however I always found looking at drawings to be too unrealistic and idealized. This book is excellent because it has hundreds of photos of actual cadaveric dissections. It is still in my library today and I reference if frequently. Caution – avoid opening this book on subways, buses, or in front of non-medical family members as the pictures are quite graphic!
  • Pulmonology Review. Good review of pulmonary physiology. This book is also helpful when you get onto the wards as well.

Years 3 and 4

For most medical students you are now entering the world of actually practicing medicine. As you start to forget all the minutia you learned about in years one and two you can actually start learning what being a doctor is actually about (prior authorizations, just kidding, sort of…).

               

That’s my list and I’m sticking to it! Although there are tons of other great books out there I felt that these books were the best for my personal learning style. If you have any books that you absolutely love and cannot live without let me know and I’d be more than happy to add them to the list or better yet drop a comment in the comments section below.

Diffuse Axonal Injury: Shearing the Cables

virtualmedstudent

Diffuse axonal injury is a form of traumatic brain injury that occurs under conditions of rapid acceleration and deceleration of the head. This frequently occurs after high impact injuries such as motorcycle crashes or high speed car accidents.

Let’s discuss a few basic brain terms before we dive into why diffuse axonal injury happens. Brain tissue is composed of neurons and glia. The neurons communicate with one another through long extensions known as axons. You can think of an axon as the telephone wire that connects one phone to another. Axons compose the bulk of what is known as “white” matter in the brain; on the other hand, “gray” matter represents clumps of neurons.

Both gray and white matter have different densities associated with them. Because of this, rapid accelerations or decelerations of the head cause the gray matter to move at a greater relative velocity compared to the white matter. If these accelerations are severe enough stretch and shear injury occurs; the end result is that the “wires” get disconnected. This, in a nutshell, is diffuse axonal injury.

Signs and Symptoms

Depending on the severity of diffuse axonal injury patients may present with different signs and symptoms. In fact, diffuse axonal injury is frequently diagnosed when patients “fail” to wake up after a traumatic event despite adequate resuscitative treatment.

In its most severe form, diffuse axonal injury results in coma. Less severe injuries may cause long term cognitive issues and personality changes.

Diagnosis

Diagnosis of diffuse axonal injury is made with an MRI scan. CT scans of the head are frequently ordered early to rule out other treatable causes for the decreased mental status often seen in patients with DAI (ie: epidural, subdural, and intraparenchymal hematomas).

The MRI will reveal restricted diffusion on diffusion weighted (DWI) and apparent diffusion coefficient (ADC) maps of the brain. Gradient echo imaging (GRE) will often show small spots of low intensity consistent with shear/stretch injury.

MRI of diffuse axonal injury

Treatment

Unfortunately, there is no effective treatment for diffuse axonal injury. There is currently no way to “re-wire” the axons. All care for diffuse axonal injury at this point is supportive.

Overview

Diffuse axonal injury occurs after rapid changes in acceleration of the head. The axons, or “wires”, between neurons get stretched, sheared and, effectively disconnected. Coma is the common presenting sign of severe axonal injury. Diagnosis is made with MR imaging. Treatment is supportive since there is currently no way to re-wire the damaged connections.

Other Stuff You Might Want to Learn About

References and Resources

  • Hijaz TA, Cento EA, Walker MT. Imaging of head trauma. J Trauma. 2010 Dec;69(6):1610-8.
  • Andriessen TM, Jacobs B, Vos PE. Clinical characteristics and pathophysiological mechanisms of focal and diffuse traumatic brain injury. J Cell Mol Med. 2010 Oct;14(10):2381-92.
  • Meythaler JM, Peduzzi JD, Eleftheriou E. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch Phys Med Rehabil. 2001 Oct;82(10):1461-71.
  • Smith DH, Meaney DF, Shull WH. Diffuse axonal injury in head trauma. J Head Trauma Rehabil. 2003 Jul-Aug;18(4):307-16.
  • Osborn AG. Osborn’s Brain: Second Edition. Elselvier, 2017.

Multiple Sclerosis: Multiple Scars in the Central Nervous System

virtualmedstudent

Multiple sclerosis literally means “multiple scars”. And in multiple sclerosis the scaring takes place in the central nervous system. The pathology of why multiple sclerosis occurs is not yet fully understood. We do know that it is an autoimmune condition in which the body attacks itself.

The target of that attack is myelin. Myelin is a fatty substance that insulates neuronal axons. You can think of myelin as the rubber coating around electrical wiring. The insulating role of myelin helps axons send information rapidly from one neuron to the next. Interestingly, multiple sclerosis only affects myelin created by oligodendrocytes, which are glial cells (ie: neuron support cells) found in the central nervous system. Multiple sclerosis does not affect myelin formed by Schwann cells, which are located in the peripheral nervous system.

The damage to myelin is thought to be caused by T-cells. T-cells are a branch of the adaptive immune system. T-cells do not normally invade the central nervous system, but in multiple sclerosis some antecedent event (possibly infection?) allows T-cells to gain access to the CNS. In genetically susceptible people these trapped T-cells "see" myelin as a foreign substance and attack it. The result is inflammation and scaring (in the brain, scaring is called "gliosis").

Signs and Symptoms

Although multiple sclerosis can occur in all races and in both genders, it tends to affect women of European descent more frequently. In addition, patients who live at higher latitudes also seem to be at higher risk.

The classic presentation of someone with multiple sclerosis is numerous neurological complaints spaced out in time. These neurological symptoms can be highly variable. Often times patients will have blurred vision or blindness if demyelination occurs at the optic nerve. This is known as optic neuritis and is a common feature in multiple sclerosis patients.

In addition, weakness of an extremity can occur and can be partial (paresis) or complete (paralysis). Difficulty speaking and swallowing can occur, as can bowel and bladder incontinence. Sensory deficits like numbness and tingling are also common. If the cerebellum or spinocerebellar tracts in the spinal cord are involved loss of coordination can occur (ataxia).

There are many other symptoms that can be seen in multiple sclerosis depending on which part of the central nervous system is involved. Ultimately, if a patient returns with several neurological complaints spaced out in time, then multiple sclerosis should be on the list of possible diagnoses.

Diagnosis

The diagnosis of multiple sclerosis is based on clinical and supporting laboratory evidence. There is no single test that can determine if it is present, but there is a set of guidelines that can help the clinician make the diagnosis, which include:

(1) Signs and symptoms referable to the central nervous system.
    (a) Symptomatic episodes should last at least 24 hours.
    (b) Two or more symptomatic episodes at least one month apart.
(2) Two or more lesions (ie: “scars”) seen on MRI of the brain (see image below).
(3) Physical exam findings supporting central nervous system disease.
(4) Cerebrospinal fluid results consistent with a diagnosis of multiple sclerosis.
(5) No other disease(s) that could explain the symptoms and findings.

MRI of Multiple Sclerosis

Many other tests are often performed to rule out other causes for the patient’s symptoms. Testing for systemic lupus erythematosis, Lyme disease, neuro-syphilis, vitamin B12 deficiency, and thyroid disease are common adjunctive tests.

Treatment

There is currently no cure for multiple sclerosis. However, like many other autoimmune disorders, there are several disease modifying medications that can slow its progression.

The first class of modifying medications are known as the "interferons". Interferon is believed to act through several different mechanisms. It inhibits white blood cell proliferation (T-cells are one type of white blood cell) and decreases antigen presentation by immune cells. It also reduces T-cell migration and switches the body towards an anti-inflammatory state. These effects help decrease the inflammation associated with multiple sclerosis. There are currently three different formulations of interferon on the market for multiple sclerosis. The first two are interferon β-1a formulations known as Avonex® and Rebif®. The third is an interferon β-1b formulation known as Betaseron®.

Another medication known as glatiramer acetate (aka: Copaxone®) acts as a possible myelin "mimick", protecting normal myelin from attack. Glatiramer is a synthetic polymer of four amino acids (ie: the building blocks of protein) found in normal human myelin. The exact mechanism of glatiramer’s actions are unknown.

Natalizumab (aka: Tysabri®) is approved for use in multiple sclerosis. It is a monoclonal antibody that binds to, and inhibits, the function of α4-integrin. α4-integrin is a cell adhesion molecule found on white blood cells that normally allows them to move into body tissues to fight infection. By blocking this movement, natalizumab is thought to decrease the number of T-cells that enter the central nervous system.

Another medication known as mitoxantrone is also used in the treatment of multiple sclerosis. It was originally designed as a cancer medication. Its mechanism of action is to disrupt DNA synthesis and repair by inhibiting a protein known as topoisomerase.

Patients who are acutely symptomatic (ie: having a "flair") are treated with intravenous steroids. Methylprednisolone is the most common steroid used in patients with acute neurological symptoms.

The goal of all of these medications is to dampen the immune response and prevent the abnormal inflammation that occurs in multiple sclerosis. Because of this, many of these medications have side effects such as the risk of infections.

Finally, depending on a patient’s symptoms, therapies designed to mitigate them may be used as well. Medications like baclofen are commonly used for spasticity; dalfampridine (Ampyra®) can help patients walk longer distances. It is important to prescribe medications that can palliate some of the symptoms.

Overview

Multiple sclerosis is an autoimmune condition in which the body attacks the myelin surrounding axons in the central nervous system (ie: the “insulation around the wires”). Symptoms are numerous and depend on what area of the brain and/or spinal cord is being “attacked”. Everything from weakness to blindness can occur. Diagnosis is based on clinical signs and symptoms, as well as supporting evidence such as MRI findings and cerebrospinal fluid abnormalities. Treatment is with various disease modifying agents as well as medications designed to treat symptoms from MS.

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Prenatal Cytogenetic Testing: MSAFP, Quad Screens, and Amniocentesis

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Prenatal Cytogenetic Testing

The goal of all prenatal testing is to determine if there are any abnormalities in the developing fetus. Not all pregnancies are "candidates" for certain forms of prenatal testing. Determining whether or not to perform invasive testing depends on many factors. Some of the common indications for invasive prenatal cytogenetic testing include:

(1) Advanced maternal age; mother will be greater than or equal to 35 years of age at time of delivery.
(2) Previous child with a genetic abnormality, especially if mother is greater than 30 years old.
(3) Known parental chromosomal abnormalities.

MSAFP

The first test that is often ordered is the maternal serum α-fetoprotein (MSAFP). The MSAFP is typically ordered between 15 and 20 weeks gestation. AFP is produced by the fetus. It crosses the placenta into the maternal blood stream where it can be measured. MSAFP can be normal, elevated, or decreased.

Elevated levels of MSAFP occur for many different reasons. Some are pathological, others are not. It is associated with neural tube defects (ie: spina bifida, anencephaly, etc.), gastrointestinal and abdominal wall problems (ie: gastroschisis, omphalocele), multiple gestations (ie: twins, triplets, etc.), fetal death, placental problems, as well as underestimated gestational age.

Depressed levels of MSAFP are harbingers of chromosomal abnormalities. The most common one is trisomy 21 (Down’s syndrome). In addition, trisomy 18 (Edward’s syndrome) is also associated with low levels of MSAFP.

Quad Screen

If abnormalities in MSAFP are detected additional maternal blood markers are measured. This is referred to as the "quad screen".

The quad screen consists of MSAFP, estriol, inhibin-A, and beta-HCG. The levels of these molecules taken together provide greater sensitivity in diagnosing chromosomal abnormalities in the fetus. For example:

Fetal Abnormality: Quad Screen Results:
Trisomy 21 (aka: Down’s Syndrome)

– Decreased AFP and estriol

– Increased β-HCG and inhibin
Trisomy 18 (aka: Edward’s Syndrome) – Decreased AFP, estriol, inhibin, and β-HCG

An abnormality in any of these markers is not 100% diagnostic of fetal pathology. In order to confirm the fetal diagnosis more invasive tests can be performed. These include amniocentesis and chorionic villus sampling.

Amniocentesis

Amniocentesis collects amniotic fluid surrounding the developing fetus. Amniotic fluid contains fetal cells that can be sent for genetic analysis. It is typically done around 15 to 17 weeks of gestation.

The procedure involves using a needle to withdraw the fluid. This is done either through the abdomen or cervix. Since amniocentesis is an invasive test there are risks. Miscarriage can occur in up to 0.5% of cases; in addition, bleeding (either maternal or fetal) can also occur.

Indications for amniocentesis Advanced maternal age (>35 years old) at time of delivery.
If quad screen was abnormal.
In cases where maternal-fetal blood incompatibility is an issue (ie: Rh-sensitization).
In cases where premature delivery may occur. Amniocentesis can be done to help determine the maturity of the fetal lungs.

Chorionic Villus Sampling

Chorionic villus sampling is another invasive test that can be used to diagnose fetal chormosomal abnormalities. It is typically done between 10 and 12 weeks of gestation. It involves sampling a piece of the chorion, which is a component of the placenta. Its main advantage is that it can be done earlier than amniocentesis; however, there is a slightly increased risk of fetal death. In addition, the diagnostic accuracy is not quite as great as amniocentesis in picking up neural tube defects.

Peripheral Umbilical Blood Sampling

Peripheral umbilical blood sampling is a process in which the fetal umbilical blood vessels are punctured so that fetal red blood cells can be obtained for analysis. This procedure is typically done in the 2nd or 3rd trimesters when there is a possibility of fetal hemolytic disease. Hemolytic diseases of the newborn occur when the mother produces antibodies that attack fetal red blood cells.

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Cervical Facet Dislocation: Houston We Have a Problem…

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The spine is composed of thirty-three bony elements referred to as vertebrae. Each vertebrae connects with the vertebrae above and below it. These connection points are referred to as “facet” joints.

Each vertebrae has two bony sections known as superior articulating processes, as well as two bony sections known as inferior articulating processes. The inferior articulating processes of one vertebrae connect with the superior articulating processes of the vertebrae directly below it; the connections are held in place by ligaments.

The combination of the superior articulating process, inferior articulating process, and ligaments that connect them together form the facet joint. This arrangement makes the joints look like shingles on the roof of a house (see image below).

Normal Facet Anatomy

Like any other joint in the body, facet joints can dislocate. This is most likely to occur in the cervical spine where the facet joints are more horizontal in orientation.

Facet joint dislocations occur under conditions of severe flexion and/or rotation. The flexion injury causes disruption of the ligaments that stabilize the joint; this allows the inferior articulating process of the top vertebrae to "jump" over the superior articulating process of the bottom vertebrae. The end result is a dislocated (aka: "jumped" or "locked") facet.

Signs and Symptoms

Roughly a quarter of patients will have no signs or symptoms if one facet joint is dislocated between two vertebrae; another quarter will have incomplete spinal cord injuries. Ten percent will be paralyzed or paretic (ie: unable to move their arms or legs) and the remaining forty percent will have injury to the nerve roots exiting the spinal column. Nerve root injuries can cause paresthesias (ie: abnormal sensations) in a dermatomal pattern, as well as decreased reflexes and muscle weakness in the muscle group that the nerve serves.

The stakes for spinal cord injury increase dramatically if both facet joints are dislocated between two vertebrae. Roughly three quarters of these patients will be paralyzed! Very few people escape bilateral jumped facets without neurological injury.

Diagnosis

X-ray jumped facet
Dislocated Facet

Diagnosis can be made with x-ray and CT imaging of the spine. The image will show the inferior articulating surface of the top vertebrae displaced anterior (ie: towards the chest) and inferior (ie: towards the feet) relative to the superior articulating surface of the bottom vertebrae.

The x-ray and CT scan to the right show a jumped facet between the fourth and fifth cervical vertebrae.

Treatment

Treatment of most facet dislocations begins with external traction. This involves placing tongs on the patient’s head and applying weight to gently distract (ie: pull apart) the spine.

Continuous x-rays are taken until the inferior articulating process of the dislocated joint is perched on top of the superior articulating process of the vertebrae below. At this point the weight is gradually reduced until the joint "pops" back into the proper anatomical position.

Since facet joint dislocations involve severe ligamentous injury, patients often require surgical intervention to stabilize the neck, even after reduction with external traction.

Overview

A dislocated facet joint occurs when the inferior articulating process of one vertebrae jumps over the superior articulating process of the vertebrae below it. This usually occurs after severe flexion and rotational injuries. Diagnosis is made on x-ray or CT of the spine. Treatment is usually with a combination of external traction and surgical fusion.

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References and Resources

  • Dvorak MF, Fisher CG, Fehlings MG, et al. The surgical approach to subaxial cervical spine injuries: an evidence-based algorithm based on the SLIC classification system. Spine (Phila Pa 1976). 2007 Nov 1;32(23):2620-9.
  • Patel AA, Dailey A, Brodke DS, et al. Subaxial cervical spine trauma classification: the Subaxial Injury Classification system and case examples. Neurosurg Focus. 2008;25(5):E8.
  • Rabb CH, Lopez J, Beauchamp K, et al. Unilateral cervical facet fractures with subluxation: injury patterns and treatment. J Spinal Disord Tech. 2007 Aug;20(6):416-22.
  • Andreshak JL, Dekutoski MB. Management of unilateral facet dislocations: a review of the literature. Orthopedics. 1997 Oct;20(10):917-26.
  • [No authors listed]. Treatment of subaxial cervical spinal injuries. Neurosurgery. 2002 Mar;50(3 Suppl):S156-65.
  • Handbook of Neurosurgery. Sixth Edition. New York: Thieme, 2006. Chapter 25.
  • Baehr M, Frotscher M. Duus’ Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. Fourth Edition. Stuttgart: Thieme, 2005.

Ventricular Fibrillation: Shock Me Baby!

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Cardiac muscle contracts in a predictable, regular pattern, which allows it to generate enough force to eject blood to the body. However, in ventricular fibrillation the heart muscle “quivers” in a rapid, irregular, and unsynchronized manner. These feeble contractions are not strong, nor coordinated enough to eject blood from the heart. As a result, cardiac output drops and the body quickly goes into cardiogenic shock.

There are numerous causes of ventricular fibrillation. The most common cause of abnormal electrical activity occurs in diseased heart tissue that has lost its normal architecture. For example, muscle damage from heart attacks or disorganized heart structures seen in cardiomyopathies can serve as abnormal areas of electrical impulse formation; these irritated areas can predispose patients to develop ventricular fibrillation.

Other causes of ventricular fibrillation include electrolyte abnormalities. For example, hyperkalemia (ie: an elevated blood potassium level) can depolarize heart muscle cells and make them more likely to "fire" an action potential. In general, any electrolyte disturbance that makes the resting potential of the cardiac muscle fiber more positive (ie: more depolarized) can cause abnormal electrical impulse formation; these abnormal impulses can degenerate into ventricular fibrillation.

Signs and Symptoms

Ventricular fibrillation is a highly fatal rhythm because the heart fails to pump blood, and more specifically oxygen, to the bodies’ organs. As a result, every organ system in the body, including the heart becomes ischemic and dies.

The rapid decline in blood flow to the brain causes people to lose consciousness. If treatment is not sought quickly the patient will have anoxic brain injury (ie: a massive global stroke), which will lead to brain death.

Diagnosis

Ventricular fibrillation is diagnosed by looking at an electrocardiogram (ECG). The ECG will show disorganized and chaotic electrical activity.

Ventricular fibrillation ECG
ECG of ventricular fibrillation

Treatment

Treatment of ventricular fibrillation is with immediate un-synchronized electrical cardioversion (ie: the paddle "thingies" they use to shock someone’s heart). The goal of shocking the heart with electricity is to reset (ie: repolarize) all the cardiac muscle fibers at the same time. From there the sinus node should theoretically take over, and reset the heart back into a normal rhythm.

If a patient survives their first episode of ventricular fibrillation they often have a cardiac defibrillator implanted. Implantable cardiac defibrillators shock the heart when they detect an abnormal rhythm.

Overview

Ventricular fibrillation is a rapidly fatal, disorganized, and inefficient “quivering” of heart muscle. It causes cardiogenic shock and organ death if left untreated. It is most commonly due to underlying heart disease seen in people with coronary artery disease, previous heart attacks, and cardiomyopathies, although other causes exist. Treatment is with immediate electrical cardioversion (ie: “shocking” the heart).

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References and Resources

  • Marcus GM, Scheinman MM, Keung E. The year in clinical cardiac electrophysiology. J Am Coll Cardiol. 2010 Aug 17;56(8):667-76.
  • Dosdall DJ, Fast VG, Ideker RE. Mechanisms of defibrillation. Annu Rev Biomed Eng. 2010 Aug 15;12:233-58.
  • Braunwald E. Hypertrophic cardiomyopathy: the early years. J Cardiovasc Transl Res. 2009 Dec;2(4):341-8. Epub 2009 Oct 7.
  • Rea TD, Page RL. Community approaches to improve resuscitation after out-of-hospital sudden cardiac arrest. Circulation. 2010 Mar 9;121(9):1134-40.
  • Schaer B, Kühne M, Koller MT, et al. Therapy with an implantable cardioverter defibrillator (ICD) in patients with coronary artery disease and dilated cardiomyopathy: benefits and disadvantages. Swiss Med Wkly. 2009 Nov 14;139(45-46):647-53.
  • Callans DJ. Out-of-hospital cardiac arrest–the solution is shocking. N Engl J Med. 2004 Aug 12;351(7):632-4.
  • Lilly LS, et al. Pathophysiology of Heart Disease: An Introduction to Cardiovascular Medicine. Seventh Edition. Lippincott Williams and Wilkins, 2020.