Dear Editor

The article by Kramer et al [1] suggests that subcortical ischaemic vascular disease is associated with subtle declines in executive functioning and visual memory, even in non-demented patients. The authors compared 27 control subjects and 12 non-demented patients, which were selected after exclusion of major depression, bipolar affective disorder, and other DSM-IV I axis disorders. We wish to contribute with personal data to this topic suggesting that, even in absence of a clinical diagnosis of depression, depressive symptoms may modulate executive dysfunctions in non demented subjects with cerebrovascular disease.

We examined 34 consecutive patients with cognitive impairment-no dementia (CI-ND) (mean + SD, age: 78.1 + 6.3, range 65-90; years of education: 4.9 + 1.7, range 3-10; Mini Mental State Examination score: 24.0 + 2.4, range 18-27). The diagnosis of CI-ND was made on the basis of a standardized multidimensional protocol including history, clinical examination, detailed neuropsychological testing, and computed tomographic scan. The presence and severity of cortical, white matter, and deep subcortical lesions and of leukoaraiosis were assessed on computed tomographic film with a standardized visual rating scale.[2] With this method, the patients were quantitatively divided in two groups (50th percentile) according to the severity of cerebrovascular disease: 17 patients had none or mild, and 17 had moderate or severe cerebrovascular disease. The 2 groups had similar age (mean + SD, age: 79.1 + 6.5 and 76.9 + 6.0; p =0.31, t-test), educational level (mean + SD, years of schooling: 4.7 + 1.5 and 5.3 + 1.9; p =0.27 t-test), cognitive impairment (mean + SD, Mini Mental State Examination score: 24.2 + 2.7 and 23.8 + 2.0; p =0.63 t- test), functional status (mean + SD, Barthel Index: 85.3 + 18.9 and 80.8 + 21.4; p =0.57, t-test), and comorbidity (mean + SD, Charlson Index: 2.1 + 2.2 and 2.2 + 1.6; p =0.95, t-test). Comparing the neuropsychological tests, we found that the patients in the group with none or mild cerebrovascular disease performed better on Babcock (mean + SD, score: 11.3 + 2.3 and 8.6 + 3.0; p =0.01, t-test), on digit symbol (mean + SD, associations in 90 seconds: 14.3 + 6.8 and 11.7 + 4.9; p =0.24, t-test), on trail making A (mean + SD, seconds: 143.0 + 82.6 and 228.2 + 157.7; p =0.05, t-test), but were significantly less depressed (mean + SD number of symptoms on Center of Epidemiological Studies-depression scale: CES-D, 10.8 + 7.2 and 18.8 + 6.6; p =0.002, t-test). However, when the effect of cerebrovascular severity on all significant variables was weighted in a multivariate linear regression model, only depressive symptoms maintained the statistical significance (CES-D: B: 0.82; confidence intervals [C.I.], 1.2-4.5; p =0.02).

Several studies have demonstrated that depressed patients have a lower performance than non depressed ones on executive functions[3]. Furthermore, the relationship between cerebrovascular disease and depression has recently been established.[4] In their study, Kramer and colleagues performed an extensive neuropsychological evaluation, but failed to take in consideration that depressive symptoms may be detected in elderly population even after exclusion of major depression. On the contrary, we suggest that depressive symptoms need to be considered in the interpretation of even subtle executive dysfunctions in cerebrovascular disease patients.

References
(1) Kramer JH, Reed BR, Mungas D, et al. Executive dysfunction in subcortical ischaemic vascular disease. J Neurol Neurosurg Psychiatry 2002; 72:217-220.
(2) Frisoni GB, Beltramello A, Binetti G, et al. Computer tomography in the detection of the vascular component in dementia. Gerontology 1995; 41:121-128.
(3) Channon S, Green PSS. Executive function in depression: the role of performance strategies in aiding depressed and non-depressed participants. J Neurol Neurosurg Psychiatry 1999; 66:162-171.
(4) Alexopoulos GS, Meyer BS, Young RC, et al. “Vascular depression” hypothesis. Arch Gen Psych 1997; 10: 915-922.

Dear Editor

Peres et al (2001) are to be congratulated for advancing the limited neuroendocrine literature on chronic migraine, a disorder with a significant attendant morbidity and a poorly understood pathophysiology.

A few points however deserve mention.

In their introduction, the authors rightly highlight that chronic migraine (CM) and major depression are strongly associated. However, in this study they do not appear to have controlled for this. There is no mention of a psychiatric interview. Although they allude to the Beck Depression Inventory in the Methods section, there is no mention in the results section of the relationship between depression and cortisol in CM. This is an important omission as overactivity of the hypothalamic- pituitary-adrenal axis with peripheral hypercortisolemia occurs commonly in people with major depressive disorder, the rates of overactivity increasing with increasing severity of depression.[1]

In addition the authors make no mention of the existing literature on serum cortisol in CM subjects. It was found that 14/48 (29%) subjects with chronic daily headache [2], the majority of whom had migraine were non-suppressors of cortisol following dexamethasone. In a second study [3], the same authors found that 44% of subjects showed either basal cortisol concentrations higher than controls or non-suppression following dexamethasone. A limitation to these 2 well designed studies is that depression scores in the CM subjects were in the depressed range. The present study by Peres et al (2001), by not excluding or controlling for depression suffers the same limitation.

Thus one can only conclude from the literature to date on CM, that hypercortisolemia is a feature of CM with co-morbid depression. One cannot however come to the conclusion that hypercortisolemia is a feature of CM alone.

References
(1) Dinan, TG (1994) Glucocorticoids and the genesis of depressive illness; A psychobiological model. British Journal of Psychiatry, 164, 365-371
(2) Martignoni E, Facchinetti F, Manzoni GC, Petraglia F, Nappi G, Genazzani AR (1986). Abnormal dexamethasone suppression test in daily chronic headache sufferers. Psychiatry Research 19, 51-7.
(3) Martignoni E, Facchinetti F, Rossi F, Sances AR, Genazzani AR, Nappi G (1989). Neuroendocrine evidence of deranged noradrenergic activity in chronic migraine. Psychoneuroendocrinology 14, 357-363

Dear Professor Kennard

I must thank you for making eJNNP free on the net for the developing countries. I was so excited by this news that I couldn't sleep the whole night and kept on browsing the JNNP site. It's indeed a great service to the neurologists of all the developing nations. I sincerely hope that the American Academy of Neurology follows suit and makes Neurology available on the net for developing nations. Could you please suggest this to them when you meet their editor?

Yours truly

Dr. A. Apte
Consultant Neurologist
Surat ,Gujarat
India

Dear Editor

We read with interest the correspondence from Wilkinson and colleagues [1]. These authors did not find any mutation in the frataxin gene in eight patients with isolated paraparesis and evidence of recessive inheritance. We agree with the authors that Friedreich ataxia is rarely revealed by isolated spastic paraparesis. We have described the first patients, presenting as isolated spastic paraparesis with abnormal GAA trinculeotide repeat expansion in intron 1 of the X25 gene [2]. In june 2001, Lhatoo and colleagues published in Neurology the same observation as our [3]. We confirm that isolated spastic paraparesis rarely reveals Friedreich ataxia. But clinicians in charge of patients with spastic paraparesis and possible recessive inheritance, without any explanation, have to search for a mutation in the frataxin gene.

References
(1) Wilkinson PA, Bradley JL, Warner TT. Friedreich's ataxia presenting as an isolated spastic paraparesis. J Neurol Neurosurg Psychiatr 2001, 71: 709.
(2) Castelnovo G, Biolsi B, Barbaud A et al. Friedreich's ataxia presenting as an isolated spastic paraparesis. J Neurol Neurosurg 2000; 69: 693.
(3) Lhatoo SD, Rao DG, Kane NM, Omerod IE. Very late onset Friedreich's presenting as spastic tetraparesis without ataxia or neuropathy. Neurology 2001, 56; 1776-1777.