AssessmentsSpinal cord disorders: Pathology review
USMLE® Step 1 style questions USMLE
A 46-year-old male is brought to the emergency department after being involved in a high-speed motor vehicle injury. The patient was the restrained passenger in a stationary vehicle as he was rear-ended by another vehicle traveling approximately 80 miles per hour. The patient’s neck was hyperflexed during the collision and now feels stiff. He is unable to move his arms or legs. Temperature is 37.0°C (98.6°F), pulse is 110/min, respirations are 9/min, blood pressure is 90/65 mmHg, and O2 saturation is 97% on room air. Neurological exam is notable for bilateral loss of pain and temperature sensation as well as bilateral loss of motor function below C6. Sensation to soft touch and vibration is unaffected. Which of the following is the most likely diagnosis?
Contributors:Megan Gullotto, MSMI, Robyn Hughes, MScBMC, Elizabeth Nixon-Shapiro, MSMI, CMI, Alex Aranda, Jake Ryan, Antonia Syrnioti, MD
At the physician’s office, 55-year-old Mario presents complaining of weakness in his hands and feet. These symptoms have gradually progressed over the past couple of months. At first, he struggled to manipulate small objects like buttoning his shirt. Now he also often stumbles while walking and recently fell down the stairs. In addition, his family mentions that his speech has become slightly slurred. He denies any sensory symptoms, memory loss or any bowel or bladder complaints. Later that day, 43-year-old Donna comes in with difficulty walking. She has fallen several times over the last few weeks. Her past medical history is significant for HIV infection, which was diagnosed a few years ago. On neurologic examination, her pupils are small and irregularly shaped and do not react to light, but constrict with accommodation. The sensations of pressure, vibration, fine touch and proprioception are also reduced throughout the lower extremities. She has a wide-based gait and cannot maintain balance with her eyes closed.
Based on the initial presentation, both Mario and Donna have some form of spinal cord disorder. Okay, let’s talk about physiology first real quick. If we zoom in at a cross-section of the spinal cord, we’ll see that it is composed of both grey and white matter. Grey matter is found within the medial portion of the spinal cord and has two dorsal or posterior horns that contain cell bodies of sensory neurons and two ventral or anterior horns that contain cell bodies of motor neurons. In the center of the grey matter there’s a small cavity called the central canal which is filled with cerebrospinal fluid that provides nutrients and mechanical support. Surrounding the grey matter is white matter, which consists of the axons of various neurons and they are organized into tracts that carry information to and from the brain.
For your exams, there are a few main tracts to remember. First, there’s the spinothalamic tract which is an ascending pathway and it’s divided into two parts. The lateral tract carries sensory information for pain and temperature, while the anterior tract carries information for crude touch, or the sense one has been touched, without being able to localize where they were touched. For this to happen, a first order neuron, found inside a dorsal root ganglion carries sensory input from the skin to the dorsal horn of the spinal cord, where it synapses with the second order neuron. And that neuron ascends 1-2 vertebral levels and decussates or crosses to the opposite side of the spinal cord via an area of white matter called the anterior white commissure. The secondary neuron then ascends up the length of the spinal cord via the spinothalamic tracts, and eventually synapse with a 3rd order neuron located in the ventral posterior nucleus of the thalamus. This 3rd order neuron then sends its axon up to the sensory cortex of the brain, letting you know that there’s a sensory signal.
Next, there are two ascending dorsal column tracts: the fasciculus gracilis which carries sensory information from the lower trunk and legs, and the fasciculus cuneatus which carries sensory information from the upper trunk and arms. These tracts both carry sensations like pressure, vibration, fine touch, which is where you can localize where you were touched, and proprioception which is an awareness of your body’s position in space. Once again, for this to occur, a 1st order neuron collects sensory information, but, in this case, ascends up along the same side of the whole length of the spinal cord to reach the lower level of the medulla oblongata where it synapses with the cell body of a 2nd order neuron in the nucleus cuneatus. The 2nd order neuron then sends off an axon that crosses over to the opposite side of the medulla, and travels up to the ventral posterior nucleus of the thalamus to synapse with a 3rd order neuron. And then, the 3rd order neuron then sends up an axon that carries the sensory signals to the sensory cortex of the brain.
Once your brain receives all that information, it may decide that it wants a muscle to contract. So, to do that, it sends a signal from an upper motor neuron in the motor cortex through a descending pathway, known as the corticospinal tract, in the midbrain and cross to the opposite side at the medulla before continuing down the spinal cord. There, it synapses with lower motor neurons in the anterior horn. The lower motor neuron then sends out an axon that synapse with the muscle it innervates. Similar to that, there’s also the corticobulbar tract. Upper motor neurons from the motor cortex travel through the corticobulbar tract to reach the brainstem and cross over to the opposite side of the pons or medulla, where they synapse directly with the nuclei of lower motor neurons that makes up the cranial nerves. And these control the muscles of the head and neck.
Now, for your exams, it’s important to know that with both an upper and a lower motor neuron lesion, the muscle won’t be able to contract, which will result in muscle weakness, or decrease in muscle power. But there are a few key facts that will help you differentiate between the two. So with an upper motor neuron lesion, muscle tone or resistance to passive stretch will be increased, also known as spastic paralysis, muscle bulk will be normal, and deep tendon reflexes will be hyperactive. And there’s also a unique feature, known as the Babinski reflex. So, normally when stroking the lateral aspect of the sole of the foot, there’s plantar or downward flexion of all toes. When there’s dorsiflexion of the big toe and fanning of the other toes, that’s called Babinski reflex. In contrast, in a lower motor neuron lesion, muscle tone will be decreased, which is known as flaccid paralysis, there’ll be muscle atrophy and deep tendon reflexes will be hypoactive or absent. And the unique feature will be fasciculations, which are small muscle twitches under the skin.
Okay, so let’s take a closer look at the different types of spinal cord disorders, starting with the ones affecting motor neurons of the two anterior horns. The first is spinal muscular atrophy, or SMA. This is actually a group of hereditary disorders that cause degeneration of lower motor neurons. For your test, remember that they are all a result of a deletion of the “survival motor neuron” gene or SMN1 gene found on chromosome 5, and are inherited in an autosomal recessive pattern. SMA type 1, also called Werdnig-Hoffmann disease, is the most common subtype, where babies often appear normal at birth and then in the first few weeks of life develop hypotonia or low muscle tone and symmetric flaccid paralysis, which is worse proximally than distally, and is initially more obvious in the legs, making it hard for them to do things like sit up. This is why they are sometimes described as “floppy babies”. They can also have weakness in the muscles involved in sucking, chewing, and swallowing. Another characteristic finding is tongue fasciculations. Over time, the diaphragm might be affected leading to breathing difficulties and eventually respiratory failure. For these reasons, remember that most of these babies survive less than a couple of years. For SMA types II, III, and IV, the only thing you need to know is that they are each successively milder and have a later age of onset. Diagnosis is done with genetic testing for the SMN1 mutation. And, though no cure is available at this time, there are some new FDA approved treatment options, including nusinersen, onasemnogene abeparvovec and risdiplam.
Next up is amyotrophic lateral sclerosis, or ALS. This is a degenerative disorder, which in many cases, is caused by a mutation in superoxide dismutase 1, which is an enzyme important for removing free oxygen radicals from neurons. So, without superoxide dismutase 1, we’re gonna have increased free radical injury, which will lead to neuron death. Now, this primarily affects the anterior horn neurons, leading to lower motor neuron signs, like symmetric flaccid paralysis with muscle atrophy, hypoactive deep tendon reflexes, and fasciculations. Now, the unique thing about the ALS is that it also affects the cortical motor neurons of the corticospinal and corticobulbar pathways, causing upper motor neuron problems like spastic paralysis with hyperactive deep tendon reflexes, and a Babinski sign. So if a test question combines signs of a lower and upper motor neuron lesion, the answer is probably ALS. Now, depending on which tract it happens to affect first, it may start with an inability to manipulate small items, or frequent falls. When the corticobulbar tracts of the cranial nerves are affected, we can have head and neck weakness, dysarthria, and dysphagia, or difficulty swallowing. And since the nuclei of these nerves are not affected, this is referred to as “pseudobulbar palsy”. Eventually, the disease might progress to involve the breathing muscles and can lead to respiratory failure and death. Now, another extremely high- yield fact is that ALS is a purely motor disorder, so keep in mind that through all this, there are no sensory or cognitive symptoms. Also, bowel and bladder function are spared. Diagnosis is mainly clinical and a new, but commonly tested treatment option is riluzole. This is a medication that’s a sodium channel blocker, but it’s unclear how it helps with ALS.
Moving on to occlusion of the anterior spinal artery, this can cause a spinal cord infarction, and can be iatrogenic, such as during surgery for aortic aneurysm repair. It may also occur as a complication of trauma, aortic dissection, thrombosis, embolism, vasculitis, and severe hypotension. For your exams, it’s important to remember that the area most susceptible to ischemia is below the level of T8. So, normally, above the level of T8, the anterior spinal artery arises from branches of the vertebral arteries, while below the level of T8, it’s only supplied by the artery of Adamkiewicz, which is a branch of the aorta. And this artery is particularly vulnerable during aneurysm repair, so if it’s traumatized, it can lead to anterior spinal artery occlusion. Now, in this case, the anterior two-thirds of the spinal cord will be more affected since these are the areas supplied by the anterior spinal artery. As a result, at the level of lesion, the lower motor neurons of the anterior horns will be damaged, causing lower motor neuron signs bilaterally, like flaccid paralysis and hypoactive deep tendon reflexes. Meanwhile, below the level of lesion, the lower motor neurons on both sides are no longer receiving signals from the corticospinal tract, so over time, there’ll be signs of an upper motor neuron lesion, like bilateral spastic paralysis, hyperactive deep tendon reflexes and a Babinski reflex. In addition to that, spinothalamic tracts on both sides will be affected, so, below the level of the lesions, individuals also have bilateral loss of pain and temperature. Bear in mind though that this does not affect the dorsal columns, so pressure, vibration, fine touch, and proprioception will be spared. Diagnosis is confirmed with spinal MRI, and there is usually no effective treatment.
Okay, now next, there’s poliomyelitis or polio for short. This is a viral infection caused by the poliovirus. For your test, remember that poliovirus is an RNA virus spread by fecal-oral transmission, meaning through contaminated food and water. It can also get transmitted via respiratory droplets when an infected person sneezes or coughs. Once the virus enters the body, it gets into mucosal cells of the small intestine and oropharynx and makes its way to nearby lymph nodes and eventually into the bloodstream. What you should absolutely remember is that in most cases, poliovirus stays there, so most individuals have no symptoms, except for maybe, unspecific signs of infections, like fever, headache, nausea and vomiting. But about 1% of the time, it will get into the interstitial muscle tissues and make its way to the neuromuscular junction where it will go on to invade the motor neuron. Once there, it will travel retrograde, meaning backwards, up through the axon to the anterior horn of the spinal cord. As infected lower motor neurons die, they will have flaccid paralysis and muscle atrophy as well as hypoactive or absent reflexes and fasciculations. Now, the important thing to highlight here is that the paralysis is asymmetric, which helps us differentiate polio from SMA and ALS, where paralysis is symmetric. On rare occasions, poliovirus can attack the brain stem and damage the motor nerves involved in speaking and swallowing. This part of the brain stem also sends motor nerves to the diaphragm and so if they get damaged, it can cause difficulty breathing. Another thing to know is that some people develop weakness decades after the initial infection, which is called post-polio syndrome. This is because when polio damages some motor neurons, other nearby healthy motor neurons form collateral branches to innervate the muscles that have lost their innervation. Now, over time, the natural process of aging causes motor neurons to die off. So when a motor neuron dies from the aging process, the muscles innervated by its collateral branches will also be affected.
Diagnosis of polio is based on the recovery of poliovirus from a stool sample or a throat swab. A lumbar puncture can be also done, where cerebrospinal fluid might have an increased number of white blood cells or poliovirus RNA. There’s no treatment for polio, but fortunately, it’s possible to prevent infection with vaccination, an extremely high-yield topic for your exams! There’s inactivated poliovirus vaccine, or IPV for short, also known as Salk vaccine which is made from dead or inactive viruses that’s injected into the muscle. There’s oral poliovirus vaccine, or OPV for short, also known as Sabin vaccine, which is a weakened strain of the live virus, also called a live attenuated vaccine. However, very rarely, poliomyelitis can develop after administration of the oral live-attenuated polio vaccine. And this is called vaccine-associated paralytic poliomyelitis.
Now, another viral infection that can affect the lower motor neurons is West Nile fever. For your test, the only thing you need to remember is that it is transmitted through mosquitoes. And, presents with fever, rash, myalgias, and meningitis or encephalitis, along with an acute asymmetric flaccid paralysis.
Next, there are central cord lesions near the central canal of the spinal cord. The most important one is syringomyelia. This occurs when the central canal of the spinal cord that houses the cerebrospinal fluid gradually expands. For your exams, the high-yield fact is that the main cause of syringomyelia is a congenital condition called Chiari malformation type I. In this condition the cerebellar tonsils slip down into the foramen magnum, which is the opening at the base of the skull. Now, the hallmark of this malformation is hydrocephalus, which is an abnormal accumulation of cerebrospinal fluid in the brain. Normally cerebrospinal fluid would flow through the four ventricles of the brain, and after the 4th ventricle, the fluid would either exit through two openings into the subarachnoid space where it’s reabsorbed or, alternatively, move down into the spinal canal. In Chiari malformations, however, the displacement of the cerebellum ends up blocking these openings. As a result, the fluid backs up within the spinal canal, eventually causing the spinal canal to widen, and this leads to syringomyelia. It’s important to know that it’s typically asymptomatic in childhood but adults may have headaches and symptoms from pressure on the cerebellum, like problems with coordination and balance. Aside from Chiari malformations, syringomyelia can also be caused by any acquired condition that blocks the flow of cerebrospinal fluid, like a spinal cord trauma, spinal tumors, and spinal cord abscess.
Regardless of the cause, the most important concept to keep in mind is that the expansion of the central canal in syringomyelia interferes with the fibers within the anterior white commissure of the spinothalamic tract. And this primarily occurs at the level of the cervical spine, usually C4-C6, leading to the bilateral loss of the sensation of pain, pressure, temperature, and crude touch in the upper extremities and back. A common term to describe the location of these defects is "cape-like" distribution. However, syringomyelia could also lead to dysesthetic pain, which is typically described as an abnormal, burning pain in the shoulder and neck regions. As the central canal cavity expands it can also knock out the lower motor neurons connected to the corticospinal tract which leads to muscle atrophy, muscle weakness, and paralysis. For your test, remember that syringomyelia classically spares the dorsal column, so sensations of pressure, vibrations, fine touch, and proprioception typically remain intact.
Now, syringomyelia can also lead to several high-yield complications. One of these is neuropathic arthropathy or Charcot joints, which is when there’s repeated trauma to the joints in the affected region since there’s no pain response. In syringomyelia, this is most commonly seen in the shoulders. Also, the widening spinal canal can also lead to changes in the spine like scoliosis, which is a sideways curvature of the spine. And these might be the only clues in a test question!
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