Essential Tremor

Ross Hauser, MD explains essential tremor and the connection to cervical spine instability.

The term “Essential tremor” generally means that your doctors do not know the cause of the tremors. Hauser’s Law states, if you do not know the cause of neurologic-like problems, if you follow the neurology (the nerve networks) many times you will be led to cervical ligament instability causing wandering cervical vertebras to compress, pinch, and herniated the vital cervical nerves. Cervical spine instability can lead to potential problems with brain physiology and movement disorders. Upper cervical instability and destruction of the neck curve also lead to jugular vein compression. This can also cause an elevation of brain pressure which can cause dysfunction of neurological symptoms.

If you want to know does somebody have an essential tremor – a neurologic disorder that causes involuntary and rhythmic shaking which most affects the hands, you could have somebody draw or try to write something. Recently I had somebody who I suspected had Parkinson’s disease. I had them write something because, with Parkinson’s disease, a clue to the disease is that you tend to take smaller steps when walking and you have micrographia which means you write (penmanship) with very small letters or characters.

In the image above we see the differences in writing when trying to draw circular shapes.

Below are learning points from a December 2022 paper published in the journal Advances in Therapy. (1)

Essential tremor is one of the most common movement disorders and is typically marked by tremors in the upper limbs but also may involve the head, voice, lower limbs, and trunk.

In the USA, affects 7 million people or 2% of the population.
Slight female predilection (57%).
Co-morbidities include hypertension, high lipids, diabetes, obesity asthma, depression, malaise and fatigue, other tremors, dystonia, and others.
Meds include Primidone, Propranolol, Benzodiazepines, Gabapentin, Topiramate, and others.
About 40% get off meds in two years.

Essential tremor is associated with many other medical conditions. A main co-condition is Dystonia. Dystonia is muscle tension and spasm in the neck, powerful enough, to twist the head and neck in contortion. Dystonia can be caused by cervical spine instability. Are there clues this is the case? Yes, in some, popping and grinding in the neck can be a clue. The constant need for chiropractic care? Other signs or symptoms associated with cervical instability such as tinnitus, migraine, tension headache, ringing in the ears, vertigo, digestive problems, head pressure, etc.

Dystonia and Essential Tremor

Here is summarized information from my article: Dystonic storms in four patients with hypermobile Ehlers-Danlos Syndrome. Here we present findings from our recently published peer-reviewed article: “Intermittent cerebral ischemia as a cause of dystonic storms in hypermobile Ehlers-Danlos syndrome with upper cervical instability, and Prolotherapy as a successful treatment: 4 case series.” The article can be read in its entirety here: Dystonic storms in hypermobile Ehlers-Danlos syndrome.

The word Dystonic describes a condition of Dystonia, which is a disorder in which your muscles spasm and contract involuntarily causing seizure-like appearances. The “storm” is as it sounds, it can be violent dangerous shaking and spasms. As with any disorder, there can be degrees of severity. Please see our article on Cervical dystonia and spasmodic torticollis treatment.

Dystonic tremor syndromes overlap with essential tremor

In our paper, we believe we have presented first-time evidence to the medical community of four cases of patients with hypermobile Ehlers-Danlos syndrome whose dystonic storms were reproduced by vascular occlusion (the mechanical blockage) of either the vertebral or carotid arteries in the neck. This condition caused intermittent cerebral ischemia (transient, temporary stroke), which was documented by cervical motion during upright transcranial doppler examination. (An ultrasound test used to measure cerebral blood flow velocity).

There are two types of dystonic tremor syndromes (DTS), dystonic tremor (DT) and tremor associated with dystonia (TAWD), and neither is understood. Dystonic tremor syndromes (DTS) likely share some mechanisms with nontremulous dystonia, and there may also be overlaps with essential tremor (ET).

In this study published November 2020 in the Journal of Neuroscience Online (2), the researchers analyzed patients with different types of tremor diagnoses.

Patients with essential tremors (8 females, 13 males).
Patients with Dystonic tremor syndromes (10 females, 12 males), including 13 patients with dystonic tremor (DT) (writer’s cramp with writing tremor) and 9 patients with tremor associated with dystonia (TAWD; cervical dystonia with hand tremor).
Tremors were analyzed using accelerometry and surface EMG of the antagonist pairs of arm muscles during posture, simple kinetic movement, and writing.
Cerebellar inhibition was performed to assess cerebello-thalamo-cortical involvement.

Let’s stop here for an explanation of the “cerebello-thalamo-cortical involvement” and then we will return to this study.

Cerebello-thalamo-cortical involvement is a distinct problem of cerebellar circuitry. Let’s look at an April 2023 paper (3) from the Department of Neurology, Columbia University, New York. Here the authors write: “Essential tremor (ET) encompasses a wide variability of phenotypic expression (observable symptoms, in other words, different types of tremors), and this may be the consequence of dysfunction in distinct subcircuits in the brain. The cerebello-thalamo-cortical circuit is a common substrate (possible place of origin) for the multiple subtypes of action tremor. Within the cerebellum, three sets of cerebellar cortex-deep cerebellar nuclei connections are important for tremor.”

Let’s stop again for some more brief explanations: This is from a December 2021 paper (4)

Intention tremor. Tremor is worse when voluntarily reaching for something.
Postural tremor. The tremor worsens when trying to hold a position. Such as arms outstretched.
Isometric tremor. The tremor worsens when trying to hold an object or holding someone’s hand.
Rest tremor: Tremor occurs in a body part that is at rest and completely supported against gravity such as a hand resting on a table. A foot-in-a-chair recliner.

Back to the Columbia University study: “The lateral hemispheres and dentate nuclei (parts of the brain that control movement) may be involved in intention, postural and isometric tremor. The intermediate zone and interposed nuclei (parts of the brain that help control balance) could be involved in intention tremors. The vermis and fastigial nuclei (the complexity of movement) could be involved in head and proximal upper extremity tremors. Studying distinct cerebellar circuitry will provide an important framework for understanding the clinical heterogeneity of essential tremor.”

Using the different types of tremors and possible origins in the brain as a guide, let’s return to the xx studies: “(This) study shows that the two dystonic tremor syndromes are distinct entities with dystonic tremor closer to nontremorous dystonia and tremor associated with dystonia (TAWD) closer to essential tremor. So what does this mean? According to the authors, it means that patients need to have their tremors better understood. They are often misclassified. Further dystonic tremor (DT) and dystonia and tremor associated with dystonia (TAWD) are distinct phenotypes, and the physiological characteristics of dystonic tremor (DT) are more similar to nontremorous dystonia, and tremor associated with dystonia (TAWD) is closer to Essential Tremor.

Tremor is involuntary and rhythmic; it is pathological. It is a chronic, progressive neurological disease whose main symptom is tremor which is typically postural or kinetic.

Essential tremor cases are seen as:

Essential tremor in the hands: 95% of patients
Essential tremor in the head: 34+%
Essential tremor in the tongue: 30%
Essential tremor heard in the voice: 12%
Essential tremor in the face and chin 7%
Essential tremor in the 5% torso.

The most common treatments

The most common treatments are substances that calm the nervous system down. Forty percent of people who get on medications for essential tremors get off of them within 2 years because they don’t work as well or they don’t work at all now. The question then becomes, if a medication is working and then all of a sudden it stops working, what is the cause of that? I would say that the reason the medication is no longer working is because your condition is progressively getting worse. What is a condition that would be considered progressive that could affect the brain? A culprit is Intracranial hypertension caused by progressively worsening cervical spine instability. If cervical spine instability is not addressed, we would expect to see progressively worsening tremors in some patients.

Propranolol, and Inderal beta blockers, block the adrenaline system, and they decrease sympathetic hyperactivity (tremors). However, there is a debate about whether this slowing down of the metabolism causes depression or makes existing depression worse.

Returning to the above December 2022 paper published in the journal Advances in Therapy. (1): “Despite being one of the most common movement disorders, essential tremor (ET) is frequently undiagnosed or misdiagnosed, undertreated, or untreated, with only one pharmacologic option approved by the US Food and Drug Administration. The undesirable side-effect profiles, high discontinuation rates, and limited efficacy associated with available pharmacological and surgical options further highlight the need for additional treatment options and a greater understanding of ET and its impact on patients in a real-world setting.” Some of the characteristics noted were:

Increases with age (7% over 65 years old and affects 11% of people over age 80).
Many have non-motor symptoms including cognitive decline, psychiatric features (apathy, depression, anxiety), sensory fears (hearing, smell), sleep dysregulation, and other disorders.
Some believe the cause is neurodegenerative (Nerve damage as discussed above and atrophy, more common in Parkinson’s, Alzheimer’s).
30% of pharmacological treatments are completely ineffective (Propranolol is about 50% effective but the two-year discontinuation rate was 40%).
Is increased by anxiety, stress, certain medications (anticholinergics or sympathomimetics), and excessive caffeine.
Classified under the conditions in which they occur: resting, action, kinetic and isometric tremor.

Deep Brain Stimulation

Some neurosurgeons will suggest to their patients that deep brain stimulators can help them with their advanced Parkinson’s and advanced tremors, doctors will put in probes. You can see in the image below that a neural stimulator is placed in the chest to help inhibit the tremor. The stimulators are put in the thalamus (that area of the brain that regulates, among many things, movement and subsequent tremors).

May help with tremors and depression

A March 2023 paper from the University of Minnesota Twin Cities Medical School and Vanderbilt University Medical Center writes (6): “Essential tremor patients present with both motor and non-motor symptoms including depression. . . Both quantitative and qualitative analyses of the existing literature suggest that deep brain stimulation of the ventral intermediate nucleus (in the thalamus) improves depression postoperatively among essential tremor patients.

There is some controversy over the placement of the deep brain stimulation.

An April 2023 paper from researchers in the United Kingdom published in the Journal of Neurology (5) wrote: “Deep brain stimulation (DBS) is an established treatment for dystonia and tremor. However, there is no consensus about the best surgical targeting strategy in patients with concomitant tremors and dystonia. Both the thalamic ventral intermediate nucleus (in the thalamus) and the globus pallidus pars interna (A part of the basal ganglia in the brain responsible for among many things, movement) have been proposed as targets.” In this study, the researchers asked, what if you inserted stimulators into both? The researchers suggested: “(Their) findings and published evidence seem to support the double-targeting approach as a safe and effective option in selected patients with tremor-dominant dystonia. ”

A February 2023 paper wrote: (7) “Globus pallidus internus deep brain stimulation is an established therapy for patients with medication-refractory Parkinson’s disease. Clinical outcomes are highly dependent on applying stimulation to precise locations in the brain. ”

The Cerebellum

Contains 10% of the volume of the brain but contains 50-80% of the neurons of the brain.
It is part of the motor system of the body.
It modifies motor commands (they don’t originate here), making the movements more accurate.
It makes postural adjustments in order to maintain balance.
Coordinates voluntary movements.
Fine-tunes motor movements (i.e. learning to hit a golf ball or baseball).

The cerebellum and tremors

We are going to examine the image below. It comes from Aiken AH, Hoots JA, Saindane AM, and Hudgins PA. Incidence of cerebellar tonsillar ectopia in idiopathic intracranial hypertension: a mimic of the Chiari I malformation. AJNR Am J Neuroradiol. 2012 Nov;33(10):1901-6. doi: 10.3174/ajnr.A3068. Copyright © 2023, AJNR Online, used with permission from: American Society of Neuroradiology.

In this image a patient with Idiopathic Intracranial Hypertension with cerebellar tonsillar ectopia of more than 5 mm. This patient ultimately underwent surgical decompression after being managed for 12 years with CSF shunt surgery procedures alone.

A (left side image) Sagittal T2-weighted image demonstrates herniation of the cerebellar tonsils with a peglike configuration and crowding at the foramen magnum.
B (right side image) Cine CSF flow study shows loss of CSF flow posteriorly at the foramen magnum (arrow).

In the image above and demonstrated better below, the brain has sagged out of the skull. When this occurs, the cerebral spinal fluid is blocked. Obstruction of the cerebral spinal fluid because of cervical spine structure breakdown and the problems it creates can be seen as primarily affecting the cerebellum and be a possible cause of tremors.

If the cerebellum has too much pressure on it, from the backup of the cerebral spinal fluid, there’s going to be dysfunction of the cerebellum and the brain’s movement inhibitory input (tremor regulation) and this can lead to movement disorders such as essential tremor or dystonia.

Eye movement and essential tremor, a sign of cerebellar dysfunction

We are going to go back to a 2003 paper from the Department of Neurology, University of Luebeck, published in the journal Brain (8) which set out to determine whether essential tremor also affects cerebellar structures involved in eye movement control.

In this paper: essential tremor

Eye movements of 14 patients with essential tremors and 11 age-matched control subjects were analyzed
Eight essential tremor patients had clinical evidence of intention tremor (tremor when moving with the intent of doing something., ie., picking up an object or reaching for something); six had a predominantly postural tremor without intention tremor.
Essential tremor patients showed two major deficits that may indicate cerebellar dysfunction:
- an impaired smooth pursuit initiation (the ability to track objects); and
- pathological suppression of the vestibulo-ocular reflex (VOR – balance and the (the understanding of where you are in your environment) time constant by head tilts (‘otolith dumping’ – the sensation of falling or tilting over).

In the step ramp smooth pursuit paradigm (a test to determine the patient’s ability to follow or pursue a moving object), the initial eye acceleration in the first 60 (milliseconds) of pursuit generation was significantly reduced in eight essential patients, particularly in eight essential (intention tremor) patients, by approximately 44% compared with that of control subjects (The eye was delayed or experienced a hesitation trying to follow an object).

Subsequent steady-state pursuit velocity and sinusoidal pursuit gain (the ability to stabilize a moving object) were also significantly decreased in essential tremor patients, whereas pursuit latency (both eyes moving in the same direction trying to follow an object)) was unaffected.

The researchers concluded: “The deficit of pursuit initiation, its correlation with the intensity of intention tremor, and the pathological vestibulo-ocular reflex (VOR) dumping provide additional evidence of a cerebellar dysfunction in the advanced stage of essential tremor when intention tremor becomes part of the clinical symptoms, and point to a common pathomechanism.”

Now let’s move ahead to the 2023 paper in the Journal of neural transmission (9). “Eye movement abnormalities were first reported two decades ago (the 2003 study we just discussed) as an atypical finding in essential tremor. Today, a growing number of publications about eye movement abnormalities in neurodegenerative diseases have helped us understand their pathophysiology and the basis of their phenotypic variability (what causes it, how it develops). Thus, addressing such aspects in essential tremors may disentangle, based on the oculomotor network abnormalities, the dysfunctional brain pathways in essential tremors.

What this paper suggests is that a distinctive phenotype of essential tremor could emerge characterized by anti-saccadic (horizontal gaze and processing) errors and a sub-cortical cognitive profile (mild cognitive impairment), consecutive to the disruption of the cerebello-thalamo-cortical loop. Reiterating what we discussed above: “The cerebello-thalamo-cortical circuit is a common substrate (possible place of origin) for the multiple subtypes of action tremor.”

The role of purkinje neuron cells – tremors and eye movement

Purkinje cells, the tree-like-looking structure in the image below, are cells of the cerebellum. They play a major role in the cerebellar circuit of motor coordination. They are the only cells that can broadcast signals out of the cerebellar cortex in their function of inhibiting or regulating movement. Here is a real-world example using eye movement which we just discussed.

For the eye to follow an object from left to right, muscles in the eye that allow the pupil to follow the object to the right must be regulated to allow that movement. Equally, muscles that try to pull the pupil back to the left, have to be inhibited, not allowed to pull the pupil to the left while you are trying to follow an object to the right.

In tremor or uncoordinated movement, the natural regulation of muscles needed to lift your hand up and the natural inhabitation of muscles trying to pull your hand back down to a resting position are off. It can be dysfunction of the Purkinje cells or it can be the loss of Purkinje cells.

In 2016, researchers at Columbia University Medical Center and the New York Presbyterian Hospital, and Yale School of Medicine, (10) found that in the brains of deceased people, post-mortem examination demonstrated a 30-40% loss of purkinje neuron cells. Thus supporting the view that neurodegeneration of cerebellar Purkinje cells is a factor in the cause and progression of essential tremors.

Is essential tremor a degenerative disorder or an electric disorder?

In March 2022, Dr. Phyllis L. Faust of the Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons and the New York Presbyterian Hospital wrote: (11) “Much debate has centered on whether essential should be considered a degenerative disorder, with underlying pathological changes in brain causing progressive disease manifestations such as in Alzheimer’s and Parkinson’s disease), or an electric disorder, with overactivity of intrinsically oscillatory motor networks that occur without underlying structural brain abnormalities.” In other words, can essential tremor be a disease of neurological dysfunction, in other words, can it be caused by influences outside of the brain? While support for the neurodegenerative grows, that essential tremor is a degenerative brain disease, Dr. Faust writes: “There are likely considerable overlaps between the degenerative and electric hypotheses for essential, including a current focus on central involvement of the cerebellum for tremor generation. There may be a future merging of aspects of these hypotheses as we begin to explore whether cellular reactions occur elsewhere within the tremor network.”

The GABA system and treatments: the GABA hypothesis of essential tremor

γ-Aminobutyric acid or gamma-aminobutyric acid or (GABA) is a main inhibitory neurotransmitter (it slows things down). One of the problems that GABA may inhibit is uncontrolled tremors. This has evolved into the “GABA hypothesis” of essential tremor.

In March 2021, Dr. Alexandre Gironell of the Movement Disorders Unit, Department of Neurology, Sant Pau Hospital, Autonomous University of Barcelona published these observations in the journal International Review of Neurobiology (x)

“Dysfunction in gamma-aminobutyric acid (GABA) neurotransmission has emerged as a prime suspect for the underlying neurochemical dysfunction in essential tremor. This dysfunction has been termed the GABA hypothesis. . . .It remains to be (understood) whether reduced GABAergic tone (dysfunction of the GABA inhibitory system) is a primary contributing factor to essential tremor pathophysiology, a consequence of altered Purkinje cell function, or even a result of Purkinje cell death. More studies are clearly needed to confirm both the neurodegenerative nature of essential tremor and the reduction in GABA activity in the cerebellum.”

References

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