Neurologist-in-training

The aim of this section is to prepare the neurologist-in-training for the FMH examination, to confront her or him with specific problems of everyday neurological practice and to give him or her updates on recent controversies in clinical neurology.

Neurological MCQ

Select the one correct answer.

References

• Browne TR, Holmes GL. Epilepsy. N Engl J Med 2001;344:1145–51.
• Rowan AJ, Ramsay RE, Collins JF, Pryor F, Boardman KD, Uthman BM, et al., and the VA Cooperative Study 428 Group. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology 2005;64:1868–73.
• Brazis PW, Masdeu JC, Biller J. Cerebral hemispheres. In: Localization in Clinical Neurology. 4th edition. London: Lippincott, Williams & Wilkins; 2001. p. 453–521.

Neuroradiology/Neuroanatomy

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Poststroke depression: certainties and uncertainties

The prevalence of a depressive episode occurring within 6–12 months after an ischaemic stroke is high, globally estimated to be about 30%, albeit with marked variability among studies.

Actually the DSM-IV-TR provides the diagnostic criteria of poststroke depression (PSD) that are universally adopted in clinical and scientific settings. These criteria correspond to “depression occurring with chronic medical conditions” (e.g. chronic heart failure, hyperthyroidism, stroke, etc.). However, the only feature distinguishing poststroke depression from endogenous depression (ED) (equivalent to depression in subjects without brain damage) is a persistent depressed mood that is judged as one of the direct consequences of a general medical disorder. Therefore, in absence of biological markers of the disease, such criteria do not provide the reason why a presupposed aetiological factor for poststroke depression (e.g. stroke) should exclude the diagnosis of endogenous depression occurring after stroke. Thus the scientific debate is still heated on the following two questions: are poststroke depression and endogenous depression similar or different diseases? Is poststroke depression conditioned by strokerelated factors (i.e. lesion location) or are the “psychological” factors (i.e. the process of coping with disability) the major determinants?

In the last five years such a debate has been even enhanced by findings of meta-analysis studies. For instance, after reviewing 35 studies (108 being excluded for methodological problems!), Carson and colleagues [1] concluded that lesion location might contribute to poststroke depression only to a small extent. Bhogal and colleagues [2], by reviewing 26 studies, found an association between poststroke depression and lesion location on the left hemisphere. However, this association might have depended either on some demographic characteristics (i.e. being inpatient) or the interval after stroke onset (i.e. assessment of depression within few weeks after stroke). Another meta-analysis by Narushima and colleagues [3], who adopted different criteria of selection, supported the relationship of proximity of lesion to the left frontal pole and PSD risk. Neuropathological data lend support to the hypothesis that psychological rather than neurological factors (i.e. stroke location) are the main determinants of poststroke depression [4]. In conclusion, the causal relationship between lesion location and pathogenesis of poststroke depression remains fundamentally unproven, and the variable lesion location has no clinical utility to determine which patients should be screened for poststroke depression.

Nevertheless, two aspects have emerged from the recent clinical research as more certain than doubtful: (1) the severity of the neurological deficit (either at admission or at the moment of the assessment) is probably the most significant predictor of PSD occurrence [5, 6]; (2) poststroke depression has a negative repercussion on the recovery of neurological deficits [7], on the functional autonomy [6] and on the quality of life of patients [8]. Furthermore, poststroke depression emerges as a main determinant of the depression of the caregiver [9], a condition found in about 30% of caregivers of stroke survivors.

These findings undoubtedly indicate that a pharmacological treatment of poststroke depression should always be considered for patients with depressive symptoms and severe deficits, even in the first weeks after stroke and before the patient is transferred to the rehabilitation centre.

Pharmacological treatment of poststroke depression might also reduce the overall risk of mortality of stroke patients [10]. Although this finding should be confirmed in future research, it should be noted that depression and depressive symptoms have been recognised as a risk factor for cardiovascular disease and, more recently, as a risk factor for stroke [11].

The recovery from depression is considered significant when it corresponds to a reduction of the score of standardised questionnaires (i.e. the HDRS or BDI) greater or equal to 50%, and the use of scales is specifically required to monitor therapeutic interventions. However, it should be stressed that reduction of depressive symptoms greater or equal to 50% might not correspond to disease remission. As generally accepted, a placebo effect may also account for 35% of the therapeutic response in trials of antidepressants.

The evidence for the efficaciousness of nortriptyline or citalopram or fluoxetine in treating poststroke depression (level of evidence: 2+) emerges from few selected studies [12–14]. Conversely, recent Cochrane reviews [15, 16] concluded that data are not sufficient to propose pharmacological treatments for both prevention and treatment of poststroke depression. However, the results of these meta-analyses have poor clinical implication, because, for the reasons reported above, depressive symptoms should always and intensively be treated in stroke patients.

Selective serotonin reuptake inhibitors (SSRI) are the first-choice drugs because of their better safety profile. According to expert recommendations, a pharmacological treatment has to be continued for at least 4–6 months.

Cognitive and behavioural therapies could be appropriate treatments, especially in those cases where depressive symptoms and patient personality have been assessed extensively, but conclusive data are not available.

In conclusion, despite the fact that much work remains to be done to better understand the pathogenesis of poststroke depression, the neurologist, who is often the primary care provider of stroke patients, must be able to diagnose early poststroke depression in order to provide early treatment and to monitor the effects of therapeutic interventions.

References

• Carson AJ, MacHale S, Allen K, Lawrie SM, Dennis M, House A, et al. Depression after stroke and lesion location: a systematic review. Lancet 2000;356:122–6.
• Bhogal SK, Teasell R, Foley N, Speechley M. Lesion location and poststroke depression: systematic review of the methodological limitations in the literature. Stroke 2004;35:794–802.
• Narushima K, Kosier JT, Robinson RG. A reappraisal of poststroke depression, intra- and interhemispheric lesion location using meta-analysis. J Neuropsychiatry Clin Neurosci 2003;15:422–30.
• Bozikas VP, Gold G, Kovari E, Herrmann F, Karvatos A, Giannakopoulos P, et al. Pathological correlates of poststroke depression in elderly patients. Am J Geriatr Psychiatry 2005;13:166–9.
• Naess H, Nyland HI, Thomassen L, Aarseth J, Myhr KM. Mild depression in young adults with cerebral infarction at long-term follow-up: a population-based study. Eur J Neurol 2005;12:194–8.
• Singh A, Black SE, Herrmann N, Leibovitch FS, Ebert PL, Lawrence J, et al. Functional and neuroanatomic correlations in poststroke depression: the Sunnybrook Stroke Study. Stroke 2000;31:637–44.
• Pohjasvaara TR, Leppavuori A, Siira I, Vataja R, Kaste M, Erkinjuntti T. Frequency and clinical determinants of poststroke depression. Stroke 1998;29:2311–7.
• Haacke C, Althaus A, Spottke A, Siebert U, Back T, Dodel R. Long-term outcome after stroke: evaluating health-related quality of life using utility measurements. Stroke 2006;37:193–8.
• Berg A, Palomaki H, Lönnqvist J, Lehtihalmes M, Kaste M. Depression among caregivers of stroke survivors. Stroke 2005;36:639–43.
• Jorge RE, Robinson RG, Arudt S, Starkstein S. Mortality and poststroke depression: a placebo-controlled trial of antidepressants.Am J Psychiatry 2003;160:1823–9.
• Gump BB, Matthews KA, Eberly LE, Chang YF. Depressive symptoms and mortality in men: results from the Multiple Risk Factor Intervention Trial. Stroke 2005;36:98–102.
• Robinson RG, Schultz SK, Castello C, Kopel T, Kosier JT, Newman RM, et al. Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study. Am J Psychiatry 2000;157:351–9.
• Fruehwald S, Gatterbauer E, Rehak P, Baumhackl U. Early fluoxetine treatment of post-stroke depression: a three-month double-blind placebo-controlled study with an open-label long-term follow-up. J Neurol 2003;250:347–51.
• Andersen G, Vestergaard K, Lauritzen L. Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram. Stroke 1994;25:1099–104.
• Anderson CS, Hackett ML, House AO. Interventions for preventing depression after stroke. Cochrane Database Syst Rev 2004;2:CD003689.
• Hackett ML, Anderson CS, House AO. Interventions for treating depression after stroke. Cochrane Database Syst Rev 2004;3:CD003437.

Neurologist-in-training

Answers to MCQ

Answers to Neuroradiology/Neuroanatomy

A 

Gyrus rectus

B 

Mamillary bodies

C 

Parahippocampal gyrus and subiculum

D 

Cerebellar vermis

P 

Multifocal cortical hyperintensities on DWI, predominant in the parietal and temporal cortex. These abnormalities were explained by profound hypoglycaemia (blood sugar unmeasurable on admission) in a patient who took an overdosis of insulin. Although anoxia and epileptic seizures may also result in cortical and/or subcortical DWI abnormalities, arterial blood gases on admission were not compatible with significant anoxia in this patient, and DWI changes related to seizures are usually less extensive. DWI hyperintensities due to hypoglycaemia may be widespread and cortical [1–3], as in this patient. They may also involve hippocampus, internal capsule, basal ganglia and middle cerebellar peduncles.

This patient improved slowly after her seizures were controlled, first showing progressive arousal, then a mutic state, followed by stereotyped verbal behaviour, irritability and defensive reactions against body care. After 3 months she was able to eat by herself and to walk a few steps, but major cognitive deficits persisted and interaction remained very limited.

References

• Holemans X, Dupuis M, Misson N, Vanderijst JF. Reversible amnesia in a Type 1 diabetic patient and bilateral hippocampal lesions on magnetic resonance imaging (MRI). Diabet Med 2001;18:761–3.
• Böttcher J, Kunze A, Kurrat C, Schmidt P, Hagemann G, Witte OW, et al. Localized reversible reduction of apparent diffusion coefficient in transient hypoglycemiainduced hemiparesis. Stroke 2005;36:e20–e22.
• Cordonnier C, Oppenheim C, Lamy C, Meder JF, Mas JL. Serial diffusion and perfusion-weighted MR in transient hypoglycemia. Neurology 2005;65:175.