Clonazepam in the treatment of essential palatal tremors.

Essential Palatal tremor (EPT) is a rare disorder presenting as unilateral or bilateral rhythmic involuntary movements of the soft palate. There is mention of the utility of benzodiazepines like clonazepam probably because of their gamma amino butyric acid (GABA) agonistic property. But no reports are available for the same. Here we report a 30-year old married female patient who presented with the complaints of pain in the lower part of face, behind the ears, back side of neck and clicking sound in her. General physical examination (GPE) revealed symmetrical rhythmic flapping movements of the soft palate and the uvula. Central nervous system (CNS) examination did not reveal any focal deficits and Magnetic resonance imaging (MRI) of the brain was normal. She was diagnosed as having EPT and treated successfully with clonazepam.

Introduction

Palatal tremor (PT) is a rare disorder presenting as unilateral or bilateral rhythmic involuntary movements of the soft palate. This condition is also called “palatal myoclonus” or “palatal nystagmus”. The movement though rhythmic like tremor, consists of repetitive rather than oscillatory movements of agonist muscles only, thus having some similarity with myoclonus. Two types of PT have been described. ‘Essential palatal tremor’ (EPT) and ‘Symptomatic palatal tremor’ (SPT). The tremors in EPT produce audible click due to the contraction of the tensor valipalatini muscle which disappear during sleep. SPT does not produce audible click and the tremors continues to be present during sleep. Simultaneous tremors of other regional structures with cranial nerve innervation may be present in SPT causing pendular oscillopsia, laryngeal involvement interrupting speech and rhythmic limb tremors.[1] The EPT has similar prevalence rates in males and females unlike SPT which is more common in males.[2] Essential tremors (ET) in general are marked by a bimodal age distribution, peaking in the second and sixth decades. Prevalence estimates for essential tremor of any anatomical site range from 0.4% to 5.6% of the population older than 40 years of age. A minority of these cases present clinically. Familial clustering of ET ranges from 17% to 100%, with autosomal dominance being the suspected mode of inheritance.[3]

Several patho-physiological mechanisms have been proposed to explain the phenomenon of PT. The different lesions which interrupt the Dentato-Rubral-Olivary pathway which is called the Guillain-Mollaret triangle have been implicated in SPT. The exact site of pathology in EPT is unclear thus indicating the two are different disease processes.[4]

EPT is a rare condition. Few case reports are available mentioning the drug treatment of EPT. The drugs used are sodium valproate,[5] flunarizine[6] and local infiltration of botulinum toxin[7] but these reports have not been replicated. There is mention of the utility of benzodiazepines in EPT in the literature but no reports are available for the same. Clonazepam has been thought to be useful in the treatment of palatal tremors probably because of its gamma amino butyric acid (GABA) agonistic property. We report here a case of EPT treated successfully with clonazepam.

Case Report

A 30-year old married female patient from a semi-urban area presented with the complaints of pain in the lower part of face, behind the ears, back side of neck which was more on the left side. It had started insidiously without any precipitating factor about three years back. Initially the illness was progressive in nature for a year and then reached plateau phase. She reported clicking sound in her ears which was even audible to people at one meter distance when she opened her mouth. The complaints would increase with the increased rate of the clicking sound. The clicking sound was louder when she opened her mouth and was not under her control. The clicking sound was absent during sleep. The symptoms did not vary with stressors at home. She also complained of poor concentration and mild impairment in work because of pain symptoms. There was no difficulty in speech and to swallow. Sleep and appetite were normal. She did not report of pervasive depressive or anxiety symptoms but she was worried about the illness. The presence of co-morbid psychiatric disorders was ruled out using MINI scale (MINI international neuropsychiatric interview, English Version 6.0.0).

General physical examination (GPE) revealed symmetrical rhythmic flapping movements of the soft palate and the uvula. She did not have associated regional tremors. A detailed central nervous system (CNS) examination did not reveal any focal deficits. Magnetic resonance imaging (MRI) of the brain was normal and did not reveal any signal changes in olivary nucleus. She was diagnosed as having EPT. She was started on clonazepam 0.75 mg /day and gradually increased to 3 mg/day over the next two months. The improvement in her symptoms started within one week and by her third visit at the end of three months, she reported an improvement of 80% in her pain symptoms and the clicking sound. Her concentration improved and reached premorbid state in all her daily activities. She was followed up for 6 months during which she reported sustained improvement. Video of the palatal tremor was taken to compare the improvement before and after administration of the medication to assess improvement.

Discussion

EPT is a heterogeneous condition which currently has no demonstrable cause and no accompanying physical or radiological signs.[4] Neurophysiological studies suggest the involvement of a central oscillator within the olivo-cerebello-thalamo-cortical circuit. This over activity may be due to impaired central inhibition and converging evidence points toward a potential role of GABA dysfunction in tremor generation.[8] The inferior olivary nucleus receives a GABA-ergic input from the dentate nucleus , red nucleus and basal ganglia. The GABAergic system inhibits electronic coupling of inferior olivary neurons, and when this pathway is disrupted may result in hyper synchronous firing of these polysynaptic neurons. The neurons of the olive are extensively coupled by gap junctions, which may relate to their capacity to oscillate when there is loss of normal GABA-ergic inhibition.[4]

Some functional studies have revealed prominent bilateral activation of the Putamen associated with EPT. These results imply a central role of the putamen in the generation of EPT.[9] One hypothesis is that tremors may arise from an imbalance between basal ganglia and cerebellar outputs. According to this theory, damaged cerebellar outflow in ET may produce an imbalance that is normalized by eliminating the surviving (tremor-generating) output from the basal ganglia.[10] It is also possible that the involvement of putamen is more common in patients of EPT than it is believed to be. clonazepam thus may act on the GABAnergic neurons of dentate nucleus, red nucleus and basal ganglia and increase the inhibition on the olivary nucleus and may lead to reduction in palatal tremors.

The pharmacological treatment for PT includes a variety of agents such as anticonvulsants like benzodiazepines, anticholinergic agents, calcium channel blockers, 5-hydroxytryptamine (5HT) and 5HT agonists (sumatriptan), nootropics (piracetam), placebos and Botulinum toxin. Relaxation techniques, voluntary mechanisms such as the valsalva maneuver and dental devices have also been attempted. The response of patients to these interventions is varied.[11] However, it is also not clear whether the same set of medications can be used in EPT and SPT which are thought to be of different etiologies.

In a study by Mahasuar et al.,[12] on possible drug induced palatal tremors, clonazepam was used in the dose of 0.5 mg/day. However the withdrawal of offending drug (lithium) and the introduction of clonazepam occurred simultaneously and thus it cannot be assumed that the reduction in symptoms was solely due to clonazepam.

Drug therapy in EPT as in any essential tremors does not cure, prevent or slow the rate of disease progression and is considered symptomatic treatment. Treatment is not required if the patient does not have significant functional or psychosocial disability. The goal is to minimize drug side effects while providing maximum improvement in function. Patients should be informed that although significant benefit may be derived, complete tremor eradication is not a realistic expectation.[13] Our case study suggests that clonazepam can be used in the treatment of EPT. However as this report is on only one patient, replication of the study result is required.

Conclusion

Clonazepam is a relatively safe and cheap treatment option for EPT.