Alcohol-Responsive Hyperkinetic Movement Disorders a Mechanistic Hypothesis PMC

The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in the chest. Alcohol is a known brain toxin, particularly to the cerebellum, which is the part involved in involuntary tremor, say the authors. Every additional year of regular daily drinking at this level upped the risk by 23 percent. Even those who drank fewer units, but who drank regularly, increased their risk, although not to the same extent. Compared with those who had not developed tremor, those who did were significantly more likely to have been drinking regularly and for longer.

• Interestingly, optogenetically-driven cerebellar oscillatory activity in wild type mice is sufficient to create tremor, demonstrating the causative relationship between abnormal cerebellar physiology and tremor [41].
• Alcohol sensitivity has been tested recently in a small group of patients using instrumental measures such as tremor accelerometry and spirography, in combination with the modified Fahn-Tolosa-Marin Scale as a clinical measure10.
• There might also be learning effects possibly reflected in tasks of the TETRAS Performance scale, which require manual dexterity, such as handwriting and spiral drawing.
• Physiological tools have been applied to measure and to quantify rhythmic movements of the limbs (i.e. tremor).

Environmental factors

Studies suggest that exposure to neurotoxic compounds such as β‐carboline alkaloids and ethanol are potential risk factors for ET, while antioxidant intake may be protective. In addition, smoking acts as a protective factor in ET, parallel to its effects in other neurological diseases. There is growing evidence to suggest that environmental and lifestyle factors play a role in ET but additional research is needed in order to completely understand their cause and effect association. There is also a need for larger case‐control and prospective cohort studies across different populations to further evaluate the etiological importance of these factors in ET. Two post-mortem studies of coeliac disease patients with cortical myoclonus have demonstrated selective loss of Purkinje cells, illustrating that isolated cerebellar pathology can generate cortical myoclonus [62,63]. In EPM-1 (Unverricht-Lundborg disease), another disorder with prominent cortical myoclonus and EtOH-response, a post-mortem study showed a similar loss of Purkinje cells with involvement of the dentate nucleus [64,65].

Outpatient Treatment

• Several environmental factors have been identified to play roles in ET, such as pesticide, heavy metals, ethanol, and β-carboline alkaloids [87].
• With proper diagnosis and treatment, many people with essential tremor are able to manage their symptoms and enjoy a good quality of life.
• The amount and frequency of alcohol consumption are also important factors to consider.

Since the converging evidence indicates the critical role of the cerebellum in ET, a recent study showed enhanced cerebellar oscillatory activity can be directly recorded by cerebellar EEG in ET patients [41]. Not only the cerebello-thalamo-cortical loop is important for ET, such loop also plays a role in parkinsonian tremor. A high density EEG study suggests that oscillatory brain activity in ET and parkinsonian tremor flows mainly from the cerebellum to the sensorimotor cortex whereas the oscillatory activity flows in the opposite direction in mimicked tremor [49]. These data demonstrate that the brain circuitry overlaps between ET and parkinsonian tremor. Another well-known β-carboline alkaloid is harmaline, and harmaline can induce acute action tremor in rodents, cats, and primates. Therefore, harmaline-induced animal tremor is considered as a classical model of ET [92].

4. Extra-cerebellar oscillatory activity

• However, ET has distinct clinical features very different from other putative cerebellar degenerative disorders.
• While there is no specific test for essential tremor, doctors may order imaging tests such as MRI or CT scans to rule out other conditions that can cause similar symptoms.
• If you have ET, you likely have been diagnosed with a tremor that has shown up without any known cause.
• These shaky hands from alcohol can be quite debilitating and embarrassing to live with.

Not only climbing fibers extend to the parallel fiber synaptic territory in ET, climbing fibers also form lateral crossing to innervate multiple Purkinje cells, and this particular pathological feature correlates with tremor severity [82]. Since Purkinje cells are GABAergic, this can lead to insufficient GABAergic neurotransmission to the deep cerebellar nuclei. However, no detailed pathological analysis of Purkinje cell terminals or synaptic numbers onto the deep cerebellar nuclei levels in the postmortem ET brain has been performed. On the other hand, a magnetic resonance spectroscopy (MRS) study did not show differences of GABA concentration in the dentate nuclei between ET patients and controls [110]. A postmortem analysis of ET dentate nuclei demonstrated reduced levels of GABAA and GABAB receptors [84], which probably predicts less responsiveness to GABAergic agents.

B: Evidence of the role of the cerebellum in alcohol-responsive movement disorders and its modulation by EtOH and GHB

For individuals with essential tremor, managing alcohol consumption requires a personalized approach to minimize the potential impact on tremors. While alcohol can affect essential tremor, the degree to which it does can vary from person to person. Here are some tips to help individuals with essential tremor navigate their alcohol consumption. Some individuals may notice essential tremor alcohol that their tremors worsen after consuming alcohol, while others may experience temporary relief or a decrease in tremor severity. The underlying causes of essential tremor are still being researched, but genetic factors appear to play a significant role. Additionally, certain environmental factors, such as chronic alcohol consumption, may exacerbate the tremors.

Personalized Approach to Alcohol Consumption

Researchers have been studying the link between alcohol consumption and essential tremor for many years. Some studies have suggested that alcohol can worsen tremors in people with essential tremor, while others have found no significant link. If you’re experiencing tremors or other unusual movements in your body and are concerned about essential tremor, it’s important to talk to your doctor.

Another related evidence of excitatory synaptic transmission involvement in ET comes from genetic studies. A GWAS identified the association of ET with SLC1A2 [124], which encodes excitatory amino acid transporter type 2 (EAAT2). EAAT2 is expressed by astrocytes to uptake excessive glutamate from excitatory neuronal transmission to prevent over-excitation. While EAAT1 is a predominant type of EAAT in the cerebellar astrocytes, EAAT2 is also expressed [125].

Responder rate for study population

Factors Impacting Alcohol’s Effect on Tremors