Migraine is associated with a higher risk of cervical carotid artery disection than of non-cervical carotid artery dissection ischemic stroke and this risk is especially evident for migraine without aura. We present a 41 year old man with persistent pain localised on entire left side of the head. Migrainous features in the presentation included: unilateral pain, throbbing quality, accompanying nausea, and photophobia. His condition later deteriorated and he developed dysphagia. MRI showed clear hyperintensity in the left medullar area and DSA demonstrated a thrombotic stenosis and left vertebral artery dissection, which was effectively treated with coil embolization

Traditional neurology has been dominated by a focus on diagnosis with accurate neuroanatomical localization of the lesion or pathophysiological definition of the underlying disease process. With some notable exceptions, such as changes in the pattern of infectious diseases in the Western world, neurological diseases have not altered much since Gowers (1888) set out the problem. The process of diagnosis, certainly for structurally based conditions, has been immeasurably served by brain imaging, first with X-ray computerized tomography and most recently with magnetic resonance imaging. Pathological study remains a cornerstone of accurate disease classification for some brain disorders, notably tumours, while the pathophysiological basis of many diseases has been elucidated by techniques including molecular biology, clinical neurophysiology and functional brain imaging. However, therapeutics in neurology can be barren, indeed neurology has often suffered the tag of being expert on diagnosis and wanting in treatment. While there can be no doubt that patients seek a label, or explanation, for their problems, treatments, indeed cures, for neurological maladies must be our aim.

Several areas of neurology have seen substantial advances in their therapeutic armamentarium in recent times and it seems appropriate to consider some of the underlying principles that drive neurological therapy and how new therapies may fit such a framework. First, some principles will be covered, after which some specific generic issues will be considered, clinical trial evaluation, dose selection, drug metabolism and interactions, and some issues of special populations.

Some principles

While everything in neurology, indeed medicine, can be individualized there are some underlying themes. The emphasis on these themes will vary with the condition being considered, and the needs of the patient. However, some part of these principles can be applied in many clinical conditions.

1. • Patients need an explanation of the condition from which they suffer and how their symptoms fit that diagnosis.

2. • Patients need to know the natural history of their condition so they can judge the likely benefit of treatments.

3. • Patients need to know the treatment options, both complementary if they exist, and orthodox.

4. • It should be made clear whether a treatment will address symptoms or the underlying disease process.

5. • Realistic goals need to be set for treatment: if the best that can be expected is a 50% improvement this needs to be stated clearly.

6. • Commonly expected or potentially serious side effects need to be stated and explained.

The human cerebral circulation is anatomically unique in its degree of extracranial to intracranial anastamoses and its need to supply a highly developed and metabolically highly dependent cerebral neocortex. The physiology of the cerebral circulation is key to understanding its pathophysiology and thus the management of patients with cerebrovascular disease. It has been covered by a number of monographs (Edvinsson et al., 1993; Mackenzie et al., 1984; Mraovitch & Sercombe, 1996; Purves, 1972; Welch et al., 1997) and particular aspects are routinely and expertly reviewed in specialized journals, such as the Journal of Cerebral Blood Flow and Metabolism. The cerebral circulation has certain key physiological features that can be clinically meaningful:

1. (i) the relationship between brain blood flow and metabolism, vasoneuronal coupling;

2. (ii) the maintenance of constant flow in the face of variations in perfusion pressure, autoregulation;

3. (iii) the effect of key respiratory gases, oxygen and carbon dioxide, on cerebral blood flow (CBF); and

4. (iv) the direct effects of nerves on the cerebral circulation, neurovascular influences on CBF.

Vasoneuronal coupling is a well-established principle (Kuschinsky, 1989), as is the fact that the brain can regulate flow in the face of changes in perfusion pressure. The effect of changes in CO2 and O2 on CBF is also an old and established concept. Neural control or neurogenically mediated changes in cerebral blood flow are a relatively recently accepted concept, although the observation that nerves exist on the vessels dates to Thomas Willis in 1664. Some established concepts will be considered here as a backdrop to the clinical discussions that follow. The classical view of the cerebral circulation has been that blood flow and cerebral metabolism are tightly coupled under the influence of substances, such as H+, adenosine, and K+ that ensure a rapid and matched supply of blood when required without neural influence. As the role of the neural innervation and its neuromodulators emerges and their functions are clarified opportunities for intervention and understanding will arise and eventually inform the management of patients with cerebrovascular disorders.

Vasoneuronal coupling

The fact that cerebral blood flow tracks closely cerebral metabolic activity remains a tenet of cerebrovascular physiology. It is the basis for many modern functional neuroimaging methods (Frackowiak & Friston, 1994).