There are several brain and spinal cord conditions that are important to consider in patients with Ehlers-Danlos Syndrome (EDS). While these conditions are considered rare in the general population, they can and do occur at higher frequency in the EDS population and can contribute significantly to the health of these patients. Additionally, they can have symptoms that overlap with those of EDS, making it more difficult and complex to create an effective treatment plan until these conditions have been adequately evaluated and addressed. These conditions include tethered cord, Chiari malformation, atlano-axial / cranio-cervical instability, and intracranial hypertension. It is important to note that not all patients with EDS have any or all of these conditions; however, because of the increased incidence within this population, I do consider and evaluate them for each of my patients with EDS.
Tethered Cord
Tethered cord syndrome (TCS) is a neurological condition that affects males and females in equal numbers. The exact incidence in the general population is unknown but it is likely to be higher in patients with EDS because of issues relating to the connective tissue at the end of the tube surrounding the spinal cord (filum terminale). Historically, the diagnosis has been controversial and the disorder often still remains unrecognized and underdiagnosed.
TCS may be congenital due to improper growth of the spinal cord during development or acquired due to tumors, spinal cord injury, infection, scar tissue, or narrowing of the spinal column with age. Infants and children with congenital TCS may have tufts of hair, skin tags, dimples, skin discoloration, hemangiomas or benign fatty tumors on the lower back as well as spina bifida.
TCS occurs when tissue attachments limit the movement of the spinal cord within the spinal column. Normally, the spinal cord ascends in the spinal canal during fetal development due to the normal differences in the rate of growth between the spinal column and the spinal cord. This causes the spinal cord to be pulled upwards so that the tip of the spinal cord reaches the normal level between T12 and L2 vertebrae by three months of age. Normally, the filum is elastic and extensible, which allows for this movement. If the filum becomes inelastic during development, then the spinal cord tip may become anchored and cease to ascend, not ascend as much as expected, or possibly ascend but under an extreme amount of tension.
Symptoms
Symptoms of TCS are due to nerve dysfunction within the spinal cord due to the stretch and tension placed on the cord. This stretching reduces the amount of oxygen reaching the nerves and creates abnormal ion channel function, leading to abnormal electrical activity within the nerves.
Specific symptoms, severity and progression of TCS vary. Symptoms may start in childhood, be slowly progressive, or are stabilized in childhood, but become apparent only in adulthood. Symptoms in children may include:
- lower back pain that worsens with activity (especially spinal stretching) and improves with rest,
- decreased leg movement, absent reflexes
- asymmetrical motor dysfunction
- leg pain, weakness or numbness,
- loss of sensation in the lower limbs,
- gait disturbances or delayed walking (“intoeing”, “loss of ankle control”)
- foot, leg, and spinal deformities or asymmetry,
- scoliosis or exaggerated lordosis,
- high-arched feet and hammertoes
- difference in leg strength
- delayed or plateau in growth
- difficulty with bladder and bowel control and repeated urinary tract infections
- possible difficulty riding a bike, prolonged bed wetting
Symptoms in adults may include:
- constant, often severe back and leg pain, which may extend to the rectum and genital area and is aggravated on flexion of lumbrosacral spine (due to stretching of lower spine); pain often described as achy, burning, heavy, stiff, or tight
- progressive sensory and motor deficits may affect the legs potentially resulting in numbness, weakness or muscle atrophy OR spasticity and hyper reflexes
- bladder and bowel dysfunction (increased frequency or urgency of urination, incontinence or constipation, frequent urinary tract infections)
Symptoms may be worse when bending slightly (e.g., over the sink), sitting with legs crossed, or holding weight at the waist level. Symptoms may also worsen for women dramatically after pregnancy.
It is also important to know that adult onset of tethered cord syndrome was considered to be rare for many years because it was believed that if an adult’s symptoms were due to a congenital tethered cord, the patient would have also had severe symptoms in childhood that lasted through to adulthood. However, this may not be the case for all patients as the progression of symptoms can vary over time.
Diagnosis
Diagnosis of TCS is based on:
- history
- signs and symptoms
- standard lumbar MRI showing low lying spinal cord (conus) and a thickened filum terminale, possibly displacement of filum, fatty filum, or lipoma
However, in patients with EDS, the standard lumbar MRI is typically normal. Additional imaging (lumbar MRI with cine) is required because the tethering for these patients is due to abnormal connective tissue, and not one of these other causes that can be visualized on the standard MRI. Because of this, these cases are known as “occult” (meaning hidden) tethered cord.
During the lumbar MRI with cine, the patient wears pulse oximeter during standard lumbar MRI setup. Instead of taking slices of images along lumbar vertebrae, the image is held at level of conus and video is taken. Video looks for motion of conus in different directions in conjunction with heartbeat. It is important that these images are evaluated by a radiologist experienced with occult TC. This lumbar with cine is essential to diagnose occult TC for patients with EDS because they have the same signs and symptoms as TCS but no abnormal findings on standard lumbar MRI.
Treatment
Treatment for TCS or occult TC is surgery to release filum terminale, and prompt surgical intervention results in reversal, or at least stabilization, of symptoms in many cases. The prior surgical method resulted in scar tissue development, which led to re-tethering and additional surgeries, and a minimally invasive option was developed and is now in use. Tethered cord may be important to treat in childhood to prevent permanent sequelae; there may be permanent effects if this isn’t treated until adulthood. Patients may also need to consider evaluation with other specialists for affected systems (e.g., gastroenterology, urology).
Naturopathically, patients can be supported with pre and post-surgery plans, treatments for affected systems, as well as the central nervous system and its connections and communication with all other systems through the body.
References
https://rarediseases.info.nih.gov/diseases/4018/tethered-cord-syndrome
https://www.ehlers-danlos.com/2015-annual-conference-files/Klinge.pdf
Chiari Malformation
Before we can talk about Chiari malformation, we need to talk about cerebrospinal fluid (CSF) and brain anatomy. CSF is special fluid made in the brain from arterial blood; it serves to cushion the brain from shocks, and as it flows around the brain and spinal cord, it brings in nutrients and carries away waste. It flows in the channels around the brain and normally, all the parts of the brain are within the skull and above the hole in the skull (foramen magnum) where the brain stem transitions into the spinal cord.
Chiari malformation occurs when the cerebellar tonsils (the bottom part of the cerebellum) drops through the foramen magnum and down into the spinal canal, compressing brainstem and blocking normal flow of CSF. This blockage can cause buildup of fluid in the spinal cord (syringomyelia or syrinx), which can destroy the tissue of the spinal column, or in the brain, causing hydrocephalus.
Chiari malformation may be considered primary if it is due to congenital abnormality (e.g., structural issues in brain, spinal cord, and/or skull) or secondary if it is due to some other cause that pulls or pushes cerebellum down. These secondary causes may include Intracranial hyper or hypotension, a cyst or tumor in the brain, or tethered cord. There is some evidence that head/neck trauma can either cause Chiari or can make a previously asymptomatic Chiari become symptomatic.
Symptoms
Symptoms of Chiari malformation can vary from person to person and do not necessarily relate to the size of tonsillar herniation (i.e., larger herniation does not necessarily mean worse symptoms). Symptoms may also be vague or nonspecific and may affect any part of the body.
Some of the most common symptoms are:
- posterior headache on exertion with neck pain
- hoarseness or swallowing problems
- sleep apnea / difficulty sleeping
- weakness or numbness in an extremity
- balance problems /dizziness
- fatigue
Symptoms can be much more extensive than this list and can be found in the references listed below.
Symptoms infants and children may be different than those in older children and adults and can include:
- Trouble feeding and swallowing
- Excessive drooling
- Noisy breathing (stridor), especially with crying
- Chronic cough
- Apnea
- Irritability, head banging and nighttime awakening (signs of headache)
- Stiff neck
- Poor arm strength (trouble crawling)
- Poor weight gain
- Scoliosis (typically unusual curves and/or locations)
Chiari causes the symptoms it does because of:
- direct compression of the cranial nerves
- direct compression of the brainstem
- direct compression of the cerebellum
- disruption of the natural flow of CSF
- elevated CSF pressure in the skull/brain (intracranial hypertension)
- damage to nerves in the spine
Diagnosis
Diagnosis of Chiari is based on assessment of:
- patient’s symptoms
- neurological exam
- MRI findings (i.e., tonsillar herniation, bone deformity, CSF blockage, syrinx)
- professional judgement on whether the patient’s signs and symptoms are caused by Chiari
Chiari malformation may take many years to be corrected diagnosed and may be misdiagnosed as MS, Fibromyalgia, Chronic Fatigue, Lupus, Migraines, Carpal Tunnel Syndrome and ALS; many patients are told they have a mental disorder.
Treatment
Treatment for Chiari depends on the evaluation by an experienced neurosurgeon who will assess the severity of the Chiari and if the malformation is responsible for the patient’s symptoms. For example, if a patient has a frontal headache that comes and goes, that is unlikely to be caused by a Chiari malformation and surgery for the Chiari would not address that symptom.
Options include:
- Watch and wait for patients with mild symptoms or in cases where Chiari was discovered incidentally on MRI
- Treat symptoms individually and supportive neck care
- Surgery with an experienced neurosurgeon
Naturopathically, patients can be supported with pre and post-surgery plans, treatments for affected systems, as well as the central nervous system and its connections and communication with all other systems through the body.
References
https://www.mayfieldchiaricenter.com
https://www.conquerchiari.org/documents/presentations/SYMPTOMS%20Presentation.pdf
Atlanto-axial / Cranio-cervical Instability
Atlanto-axial instability (AAI) occurs when there is excessive movement between the atlas (the first cervical vertebra, C1) and the axis (the second cervical vertebra, C2). Cranio-cervical instability (CCI) is a more generalized term that includes any excess movement between the skull (cranium) and the neck (cervical spine). Both occur when the ligaments between C1 and C2 or between the skull and the spine are too loose and don’t restrict unsafe movement. This laxity causes symptoms by stretching the lower cranial nerves, stretching and kinking the vertebral arteries (causing blood supply problems), and deformative stretching or deformation of the brainstem and upper spinal cord.
Risk factors for developing CCI include:
- Physical trauma [both acute (whiplash) and chronic repetitive (turning the head); possibility of chronic head forward positions]
- Inflammatory disease
- Congenital disorders
- Neoplasms
- Hereditary connective tissue disorders (including EDS)
It is not unusual for CCI to co-occur with other structural neurological abnormalities such as AAI and Chiari malformation. There may also be changes to the odontoid, which is a part of the C2 vertebra that normally projects upward through C1. These changes can include thickening of the capsule around the odontoid or misalignment of the odontoid; in both cases, the odontoid can compress the brainstem. In severe cases of laxity, the skull may sink downward onto the spine (cranial settling). All of these situations can have significant impacts on the functioning of the brain, especially the brainstem.
Symptoms
Symptoms of CCI are primarily headache and those of dysautonomia due to impacts on the brainstem. The headache is often described as a heavy, constant to near constant headache, and feeling like the head is too heavy for the neck to support (feeling like a “bobble-head”). The headache may also be described as a pressure headache that is worse with yawning, laughing, crying, coughing, sneezing or straining. This characteristic of the headache is due to the impairment of CSF flow due to the misalignment, which results in increased intracranial pressure (intracranial hypertension).
Symptoms of dysautonomia may include:
- tachycardia
- heat intolerance
- orthostatic intolerance
- syncope
- polydipsia
- delayed gastric emptying
- chronic fatigue
Other symptoms that have been reported with CCI include:
- neck pain
- central or mixed sleep apnea
- facial pain or numbness
- balance problems
- muscle weakness
- dizziness and vertigo
- vision problems
- nausea and vomiting
- impaired coordination
- paralysis
- downward nystagmus
- tinnitus and hearing loss
- reduced gag reflux and difficulty swallowing
- slow development of moving skills
- learning difficulties
- clumsiness
Diagnosis
Diagnosis of AAI/CCI may be done by several different methods. Patients can be evaluated by upright dynamic MRI with flexion/extension views. The radiologist will assess different angles between landmarks on the skull and cervical bones to identify excess movement. The challenge with this method is the limited number of upright MRI locations and the difficulty with patients being able to remain still enough in the upright position for the duration of the imaging so as not to blur the images.
Patients can also be assessed by an in office manual traction test, which if positive, can be followed by a trial of home traction with symptom monitoring. Because AAI/CCI causes significant amounts of compression at the brain stem, traction alleviates that compression and may relieve symptoms temporarily. If patients experience relief during their trial, this may indicate that a further evaluation by an experienced neurosurgeon is warranted.
The gold standard for definitive diagnosis is Invasive Cervical Traction (ICT). This is an inpatient procedure where the patient’s head is pulled upward by a pulley system. If, over the course of 48 hours, the patient’s symptoms are cleared, then CCI is confirmed.
Treatment
Treatment for AAI/CCI is multi-leveled. The first line of treatment may include:
- an adjustable C spine immobilizer (used for only certain amount of time during the day as assess for each patient)
- soft neck brace for sleeping
- physical therapy specifically to strengthen postural neck muscles
- home traction plan that is individualized to patient
- avoidance of activities that provoke exacerbation of symptoms (e.g. trampoline)
Prolotherapy injections into the lax ligaments may be considered. However, results may be variable as prolotherapy works by stimulating the body to create new connective tissue in the area of the injection, assuming that the body will generate healthy connective tissue in response to the mild irritant. If the patient has EDS, then the connective tissue that the body produces may still be too lax to create stability in the area.
If these treatments are not successful and the patient has a severe headache and worsening function, fusion surgery with an experienced neurosurgeon may be needed.
Naturopathically, there are supplements that help reduce joint hyperextensibility, which may help reduce laxity at the cranio-cervical junction. Acupuncture and aroma acu-therapy can also be used to help balance between loose joints and tight muscles. Patients can also be supported with pre and post-surgery plans if surgery is needed. Dysautonomia symptoms may require a separate naturopathic treatment plan as they can be significant for some patients.
References
http://www.thepainrelieffoundation.com/craniocervical-instability/
http://thezebranetwork.org/craniocervical-instability
Intracranial Hypertension
Intracranial hypertension (IH) is defined as higher than normal pressure of the CSF within the spaces that surround the brain and spinal cord. It is generally caused by increased production of CSF, blockage in flow, and/or increased resistance to re-absorption. It can cause both rapid and progressive vision loss and blindness as well as severe pain, most commonly as a chronic headache, which may be unresponsive to the most potent pain medication.
There are two main types of IH: acute and chronic. Acute IH is typically due to a severe head injury or intracranial bleeding from aneurysm or stroke. There is a very rapid onset after the initial injury and it causes extremely high intracranial pressure.
Chronic IH, on the other hand, is due to gradually increased CSF pressure and the pressure remains elevated over a sustained period of time. Chronic IH is divided into primary (idiopathic) and secondary. Idiopathic IH (IIH) is most common in women between the ages of 20 and 50 and BMI of greater than 30 is an additional risk factor. However, anyone can develop chronic IH, regardless of age, gender, ethnicity, race or body type. Patients with IIH may be asymptomatic for years before diagnosis, and it can occur spontaneously, without any identifiable cause to the increased intracranial pressure.
Causes of secondary IH may include:
- Head trauma [including post-traumatic brain injury (TBI)]
- Physical obstruction due to stroke, blood clots, Chiari malformation
- Kidney or liver failure
- Sleep apnea
- Lupus
- Sarcoidosis
- Hypoparathyroidism
- Addison’s disease
- Steroid withdrawal
- Behcet disease (inflammatory vasculitis)
- Certain medications
- Infections
There may also be an increased risk for IH in patients with EDS because of some of the metabolic changes seen in EDS. There may also be associations between IH and certain hormones, including estrogen, testosterone, and cortisol.
Symptoms
There are three characteristic symptoms associated with IH:
- Severe headache
- Visual changes due to swollen optic nerves (papilledema)
- Whooshing noise in one or both ears that is correlated with the pulse (pulse-synchronous tinnitus)
While these three symptoms occur most frequently, it doesn’t mean that every person will have all of them and other symptoms do occur.
The headache is the most common symptom, may awaken patients, and may be daily. The pain may slowly increase in intensity, and is pulsatile in the majority of patients. The headache of IH is often different from other headaches and may exist with other headache disorders.
Papilledema is usually symmetric and causes transient episodes of visual loss (usually < 30 seconds) that may be precipitated by postural change or Valsalva. Vision recovers to baseline after the episode. It causes progressive visual field loss possibly due to compression of the optic nerve from the elevated pressure. Tinnitus is often unilateral, and compressing the jugular vein or turning the head to the same side as the sound may make it resolve.
Other symptoms may include:
- Pain in the arms, legs and back: Sharp, deep nerve pain in the arms, shoulders/upper back, hips/ lower back, and legs
- Severe neck stiffness: An extremely painful stiff and sore neck that is hard to move. May be due to high intracranial pressure transmitted from the head down the spine, causing spinal nerve sheaths to stretch at the point where the spinal nerves exit the spinal cord and enter muscle tissue.
- Dizziness, lightheadedness, balance problems, difficulty walking
- Parasthesias (numbness/tingling in hands, feet, face)
- Nausea/vomiting
- Spinal fluid leakage from the nose or ears is a result of high intracranial pressure
- Endocrine problems due to flattening of pituitary gland and empty sella syndrome.
- Malaise and fatigue
- Depression
- Memory difficulties: short-term memory problems and trouble spelling and recognizing words are most prominent
- Exercise intolerance
Signs
For patients with IH, imaging findings may include:
- Empty sella on MRIs, CT scans and skull X-rays. Chronic IH can cause the pituitary gland to flatten against the skull bone, which gives the appearance that the sella turcica is empty.
- Posterior scleral flattening on a CT or MRI scan
Diagnosis
Diagnosis of IH is based on a patient meeting the “Dandy criteria” as follows:
• have signs and symptoms of increased intracranial pressure, such as papilledema and headache;
• have no localizing findings on neurological examination;
• have a normal MRI/CT scan with no evidence of venous obstructive disease;
• have high intracranial pressure of 250mm (25 cm)/H2O or above on a spinal tap, with no abnormalities of cerebrospinal fluid;
• are awake and alert; and
• have no other cause of increased intracranial pressure found.
These criteria rely heavily on the spinal tap (lumbar puncture) findings but there are some cautions to using this finding. First, the lumbar puncture pressure will be different if patient is laying face up, face down, or on their side, or sitting when the measurement is taken. Second, falsely high and low values can occur in normal testing conditions. Third, CSF pressure fluctuates through the day and may be normal at times. Based on these cautions, there are some researchers who feel that a single normal CSF measurements does not exclude IH as a diagnosis for a patient who meets the other criteria. Additionally, there have been cases of patients with signs and symptoms of IH who responded to treatment but who had normal pressures on lumbar puncture. There also needs to be special caution with patients with EDS as the process of lumbar puncture can lead to CSF leaks, even when done correctly.
Patients should also be evaluated by a neuro-ophthalmologist, especially if they have any indications of visual changes.
Treatment
Treatment for IH should start with treating any underlying causative factors (e.g., Chiari malformation). If none can be identified, several different medications can be used to reduce CSF production in the brain. If medications do not work well enough or if side effects are intolerable, surgery with an experienced neurosurgeon may need to be considered. Unfortunately, there aren’t any natural methods that have been proven to reduce CSF production in patients.
References
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847593/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908600/
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