Do We Belittle Essential Tremor by Calling It a Syndrome Rather Than a Disease? No

Abstract

A task force of the International Parkinson and Movement Disorder Society (MDS) recently published a tremor classification scheme that is based on the nosologic principle of two primary axes for classifying an illness: clinical manifestations (Axis 1) and etiology (Axis 2). An Axis 1 clinical syndrome is a recurring group of clinical symptoms, signs (physical findings), and possibly laboratory results that suggests the presence of at least one underlying Axis 2 etiology. Syndromes must be defined and used consistently to be of value in finding specific etiologies and effective treatments. The MDS task force concluded that essential tremor is a common neurological syndrome that has never been defined consistently by clinicians and researchers. The MDS task force defined essential tremor as a syndrome of bilateral upper limb action tremor of at least 3 years duration, with or without tremor in other locations (e.g., head, voice, or lower limbs), in the absence of other neurological signs (e.g., dystonia, parkinsonism, myoclonus, ataxia, peripheral neuropathy, and cognitive impairment). Deviations from this definition should not be labeled as essential tremor. Patients with additional questionably-abnormal signs or with signs of uncertain relevance to tremor are classified as essential tremor plus. The MDS classification scheme encourages a thorough unbiased phenotyping of patients with tremor, with no assumptions of etiology, pathology, pathophysiology, or relationship to other neurological disorders. The etiologies, pathology, and clinical course of essential tremor are too heterogeneous for this syndrome to be viewed as a disease or a family of diseases.

Keywords: classification; diagnostic axes; essential tremor; syndrome; tremor.

Figure 1

This flow diagram illustrates how Axis 1 and 2 classifications may change over time. This clinical scenario is based on the work of Chen et al. (40). A 54-year-old Chinese man presented with a 5-year history of tremor in the head and upper limbs. His family history was consistent with autosomal dominant inheritance. His initial Axis 1 classification was ET, and his Axis 2 classification was idiopathic familial. Over time, his Axis 1 classification changed from ET to ET plus mild cognitive impairment, and his Axis 1 classification ultimately changed to a combined tremor-dementia syndrome with antecedent ET. His MRI brain revealed diffusion-weighted abnormality in the subcortical U-fibers of both frontal lobes, and genetic testing revealed a GGC repeat expansion in NOTCH2NLC. Thus, his Axis 2 diagnosis was ultimately neuronal intranuclear inclusion disease that presented initially as ET.