Supplementary Online Materials

Additional Clinical History:

The patient, a right-handed Caucasian woman, reported bilateral arm tremor, beginning at age 5. Tremor worsened during adulthood and, at age 75, she was evaluated by a movement disorders neurologist (R.P.) at University of Kansas Medical Center. Her chief complaint was difficulty eating due to hand tremors. Medications werepropranolol 60 mg QD, valium 2mg prn, fosamax 70 mg per week, and synthroid 0.075 mg QD. She complained of frequent spills while attempting to eat solid foods (e.g., peas), inability to use a spoon because of spilling, avoidance of eating in public, and difficulty dialing a telephone and typing due to tremor. She reported >50% reduction in tremor on propranolol. She consumed <1 alcoholic beverage per week.She had had hip replacement surgery at age 73 and used a hearing aid. She reported mild arm tremors in her maternal grandmother, one of two brothers, and both children (daughters), though none of these carried diagnoses of essential tremor (ET). On examination, which was conducted while she was being treated with propranolol (60 mg/day), there was mild head tremor without dystonic features, no voice tremor, and mild kinetic tremor (left arm greater than right) with tremulous handwriting. The remainder of the neurological examination was normal, except for mild difficulty with tandem gait. There was no dysarthria, intention tremor, dysdiadochokinesia, or frank ataxia. There was no bradykinesia, rigidity, rest tremor, or limb dystonia. Mini-Mental State Exam (MMSE)[2] was 28/30. Aclinical diagnosis of ET was assigned.

She had previously enrolled as a donor in the Essential Tremor Centralized Brain Repository at Columbia University and, at age 73, had been evaluated by questionnaire. There had been no exposure to medications with cerebellar cytotoxicity (e.g., diphenylhydantoin). On neurological examination, while treated with propranolol (60 mg/day), there was no rest or postural tremor. Kinetic tremor of the arms ranged from mild to moderate. There was clear side-to-side head tremor without dystonic features. Rapid alternating movements, facial expression and speech were normal. Based on these data, a movement disorders neurologist (E.D.L.) diagnosed ET using standardized, published criteria[4].Handwritten spirals from both daughters revealed mild tremor in one of them (age 52); she could recall having tremor when she was in her late teens.

She wasevaluated by a general neurologist who confirmed her ET diagnosis and saw her in follow-up several times per year. Primidone (50 mg BID) and gabapentin (300 mg TID)resulted in partial tremor reduction. At age 79, her family reported that she had become easily confused and disoriented and was experiencing memory problems. In her assisted living residence, she had stopped going to the dining room to eat due to her shaky hands. She was briefly admitted to a local hospital for dehydration due to poor oral intake. Her MMSE was 15/30 and tremor in her arms and head were marked. She died two weeks later, at age 79, of myocardial infarction.

Additional Discussion:

Several clinical features merit additional discussion. First, our patient had kinetic tremor but no postural tremor. Although often defined as a postural tremor, in most ET cases, the amplitude of kinetic tremor is greater than that of postural tremor [1] and, in 20 – 30% of ET cases, there is only kinetic tremor and no postural tremor [5]. Second, when presenting to the University of Kansas, the patient reported more difficulty than one would expect based on her neurological examination at that time. The reasons are not clear but one possibility is that her tremor was partially relieved with propranolol and her complaint may have reflected past as well as current difficulty. Second, it is not uncommon for there to be a dissociation between patient’s self-reports and clinician’s ratings of function, with patients both over- and under-estimating dysfunction[3].

References

1.Brennan KC, Jurewicz EC, Ford B, Pullman SL, Louis ED (2002) Is essential tremor predominantly a kinetic or a postural tremor? A clinical and electrophysiological study. Mov Disord 17: 313-316.

2.Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189-198.

3.Louis ED, Barnes L, Albert SM et al. (2001) Correlates of functional disability in essential tremor. Mov Disord 16: 914-920.

4.Louis ED, Faust PL, Vonsattel JP et al. (2007) Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain 130: 3297-3307.

5.Louis ED, Ford B, Wendt KJ, Lee H, Andrews H (1999) A comparison of different bedside tests for essential tremor. Mov Disord 14: 462-467.

1