Neurology -- Correspondence for Louis et al., 59 (10) 1631-1633

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Correspondence published:

Reply to Letter to the Editor: Elan D Louis, Steven M Bromley, Eva C Jurewicz and Dryden Watner (9 April 2003)

Olfactory dysfunction in essential tremor: A deficit unrelated to disease duration or severity: Christopher Hawkes, Mussadiq Shah and Leslie Findley (9 April 2003)

Reply to Letter to the Editor 9 April 2003

Elan D Louis
College of Physicians and Surgeons Columbia University New York NY,
Steven M Bromley, Eva C Jurewicz and Dryden Watner
Send Correspondence to journal:
Re: Reply to Letter to the Editor

edl2{at}columbia.edu Elan D Louis, et al.

We thank Hawkes et al. for their comments, which will allow us to further describe the study design. They expressed concerns about diagnostic validity. The diagnostic procedure was stringent. ET patients were initially diagnosed by their treating neurologists, the majority of whom were movement disorder specialists at the Neurological Institute. Their clinical charts were then reviewed by a movement disorder specialist (E.D.L.) and patients with signs of dystonia, bradykinesia, or rigidity were excluded. They were then interviewed, examined (including a detailed evaluation for action tremor [1] and a Unified Parkinson's Rating Scale) and videotaped. This videotape was reviewed by a movement disorder specialist (E.D.L), and patients with rigidity, bradykinesia, dystonia, or pure upper limb postural tremor were excluded (n = 2). All met criteria for ET published by the Movement Disorder Society.[2] They also met the Washington Heights Inwood Genetic Study of ET diagnostic criteria for ET,[1, 3] which are recognized and used by investigators in diverse settings.[1, 4, 5} These criteria are unique in three regards. First, their reliability has been demonstrated.[6] Second, they have been validated against quantitative computerized tremor analysis-derived diagnoses.[1] Most important, these criteria were specifically designed to minimize the inclusion of individuals with enhanced physiological tremor, which is highly prevalent. [3] They do so by specifying the number and types of activities during which kinetic tremor must be present in order to qualify for a diagnosis of ET. In this regard, the criteria are particularly useful for population-based, familial aggregration, and epidemiological studies. Subjects were assessed for acute and chronic nasal sinus disease and were not tested if these were present. For research purposes it is preferable not to exclude patients with sporadic forms of ET or patients whose age of onset falls outside of a narrowly- defined range. Familial forms and young onset forms of neurodegenerative diseases often differ substantially from sporadic forms. Differences occur in disease etiology, underlying pathology, clinical characteristics, risk factors, and prognosis. Therefore, exclusion of sporadic and later onset cases results in the selection of a small, non-representative subsample of patients. Such an approach is prone to selection bias. While poor sniffing may result in reductions in UPSIT scores in elderly subjects, cases and controls were of similar age. We agree that it is premature to ascribe the olfactory dysfunction in ET to cerebellar pathology and, as noted in the paper, additional possibilities include a disorder of olfactory pathways in ET.
References:
1. Louis ED, Pullman S. Comparison of clinical and electrophysiological methods of diagnosing essential tremor. Mov Disord 2001;16:668-673.
2. Deuschl G, Bain P, Brin M and ad hoc Scientific Committee. Consensus statement of Movement Disorder Society on Tremor. Movement Disorders 1998;13 (Suppl 3):2-23.
3. Louis ED, Ottman RA, Ford B, et al. The Washington Heights Essential Tremor Study: Methodologic issues in essential-tremor research. Neuroepidemiology 1997;16:124-133.
4. Shukla G, Bhatia M, Pandey Rm, Behari M. Peripheral silent periods in essential tremor. J Neurol Sci 2002;199:55-58.
5. Farrer M. Gwinn-Hardy K, Muenter M et al. A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor. Human Molecular Genetics 1999;8:81-85.
6. Louis ED, Ford, Bismuth B. Reliability between two observers using a protocol for diagnosing essential tremor. Mov Disord 1998;13:287-293.

Olfactory dysfunction in essential tremor: A deficit unrelated to disease duration or severity 9 April 2003

Christopher Hawkes
Oldchurch Hospital Romford UK,
Mussadiq Shah and Leslie Findley
Send Correspondence to journal:
Re: Olfactory dysfunction in essential tremor: A deficit unrelated to disease duration or severity

chrishawkes{at}msn.com Christopher Hawkes, et al.

The paper by Louis et al. is a welcome addition to the literature on olfaction in movement disorder in general and specifically to the only previous paper on essential tremor [1]. The authors claim to have found mildly impaired olfaction in a significant proportion of ET patients and suggest this may relate to cerebellar dysfunction. If this is correct it is clearly important, as there is a possibility [which we are exploring] that olfactory testing may differentiate ET from the tremor of idiopathic Parkinson's disease (PD) but if both disorders are associated with hyposmia then smell testing would be less valuable.
Is not clear how carefully defined were those in the tremor group and whether they fulfilled any recognized criteria for ET [2]. It is also not certain how thoroughly the authors have excluded nasal/sinus disease or cerebrovascular disorder, any of which could affect smell sense particularly in an elderly population. Patients with pure upper limb postural tremor may have either early PD or typical ET and currently imaging is needed to differentiate these patients.
For research purposes it is preferable to incorporate only those with tremor going back to childhood and ideally include only those with a family history of ET[3]. It is recognized that some 30% patients with apparent ET have features of parkinsonism such as rigidity or cogwheeling [4]. This may relate to coincidental age related change or it could represent an overlap syndrome but they should be excluded or at least addressed separately. There are further problems in patients with dystonic head or limb tremor. Not only is this easily confused with ET but also little is known as yet about olfactory function in this condition.
No allowance is made for the effect of sniffing. As shown by Sobel et al. poor sniffing can result in reduction of up to four points on UPSIT-40 and place a normosmic patient in the abnormal range. Once more this is an important variable in elderly subjects.
Finally, we consider it premature to suggest that the cerebellum is the cause of possible olfactory dysfunction in ET even though there are fMRI studies to suggest a role of the cerebellum in olfaction and cognitive function. Evidence is strong for cerebellar disease as a cause of tremor but there is considerable pathological evidence of damage in the classical smell pathways in parkinsonian syndromes [5] and connections from primary olfactory areas to the cerebellum are indirect.
References:
1. Louis Elan D, Bromley Steven M, Jureqicz Eva C, and Watner Dryden. Olfactory function in essential tremor. A deficit unrelated to disease duration or severity. Neurology 2002;59:1631-1633.
2. Busenbark KL, Huber SJ, Greer G, Pahwa R and Koller WC. Olfactory function in essential tremor. Neurology 1992;42:1631-1632.
3. Deuschl G, Bain P, Brin M and ad hoc Scientific Committee. Consensus statement of Movement Disorder Society on Tremor. Movement Disorders 1998;13(suppl 3):2 -23.
4. Bain P, Findley LJ, Thompson PD. A study of hereditary essential tremor. Brain 1994;17:1-15.
5. Rajput AH, Rozdilsky B, Ang L, Rajput A. Significance of parkinsonian manifestations in essential tremor. Can J Neurol Sci 1993;20:114-117.
6. Hawkes CH, Shepard BC and Daniel SE. Is Parkinson's disease a primary olfactory disorder? Quarterly Journal of Medicine 1999;92:473-480.