The diagnosis of Parkinson's disease is predominantly clinical, based on a combination of the cardinal features of tremor, bradykinesia and rigidity. The differential essentially lies between other conditions resulting in tremor, of which essential tremor is the commonest, and other akinetic-rigid syndromes. These include progressive supranuclear palsy, multiple system atrophy, toxins and other degenerative disorders, including diffuse Lewy body disease and corticobasal degeneration. The key clinical features of these disorders and a practical diagnostic approach are briefly reviewed in this article.

The electroencephalogram (EEG) plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. Emerging evidence suggests that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug withdrawal. Continuous EEG video telemetry monitoring has an established role in the diagnosis of non-epileptic pseudo-seizures and in localizing the seizure focus for epilepsy surgery. Newer tools such as EEG mapping and magneto-encephalogram, although still investigational, appear potentially useful for defining the seizure focus in epilepsy. This review examines the traditional concepts of clinical EEG in the light of newly available data.

Controversy over the etiology and pathogenesis of Parkinson's disease (PD) has continued for many years and while the details have changed, the uncertainty persists. Although heritability was most emphatically refuted a decade ago by many investigators, recent progress firmly indicates that genetic factors at least play a role, although probably to a variable degree from one individual to another. Evidence for a variety of other etiological factors is amassed from epidemiological studies, animal models, molecular and cellular biology. Genetic factors, infectious and immunological abnormalities, the effects of ageing, toxins (endogenous as well as exogenous) and other environmental factors may all contribute to the development of PD. Loss of nigral dopaminergic neurons may be mediated by varying combinations of oxidative free radical toxicity, impaired mitochondrial function, “weak excitotoxicity” and abnormal handling of cytoskeletal proteins, all of which may shift the balance regulating apoptotic cell death.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly and an increasingly significant health concern in our aging population. In the past 10 years, our understanding of this disease has increased dramatically. While the discovery of three rare genetic mutations that can cause AD has provided much information about the causes and progression of the disease, a great deal of attention has been focused on apolipoprotien (ApoE) because of its involvement in the more common, later onset form of AD. Due to the rapid pace of recent advances, it has not been easy for health care professionals, researchers and the general public to keep abreast of these developments. This paper reviews recent research in ApoE and late-onset AD, emphasizing molecular neuropathological, genetic and neuroimaging findings and highlighting current controversies that remain to be addressed.

Serotonin receptors are highly heterogeneous and they have been regrouped within seven different families (5-HT1 - 5-HT7). With the exception of the 5-HT3 which is a ligand-gated ion channel, all others are G-protein coupled receptors with each family sharing structural, pharmacological and transductional characteristics. 5-HT receptors have been implicated in the regulation of several psychiatric and neurological disorders related to serotonergic neurotransmission, and specific receptor subtypes have recently been associated with either the pathogenesis or the treatment of migraine headache. In this respect, activation of vascular 5-HT2B and/or 5-HT7 receptors, possibly as a consequence of the sudden rise in 5-HT levels reported at the onset of a migraine attack, would hypothetically result in dilation of cerebral blood vessels and concomitant activation of sensory trigeminovascular afferents, hence initiating the manifestation of head pain. At this stage in the migraine process, activation of specific subtypes of 5-HT1 receptors has proven clinically effective in relieving migraine pain. Neural 5-HT1D and/or 5-HT1F receptors localized pre-junctionally on trigeminovascular afferents appear to mediate the triptan-induced inhibition of the neurogenic inflammatory response, with possible additional sites of action for brain penetrant 5-HT1 receptor agonists in inhibiting the transmission of pain centrally. In contrast, activation of vascular 5-HT1B receptors would constrict meningeal vessels hence recovering their pre-migraine diameter. The recent availability of subtype selective 5-HT1D and 5-HT1F receptor agonists should allow a further test of the neural/vascular hypothesis and could possibly lead to antimigraine drugs with a safer cardiovascular profile.

The management of Parkinson's disease has undergone recent changes with the advent of new therapies, both pharmacotherapy and surgery. Available interventions are discussed. Levodopa remains the mainstay of therapy. New drugs include the dopamine agonists and COMT inhibitors. New dopamine agonists which may have a levodopa “sparing effect;” it has been suggested that some of the drugs should be considered as first line treatments for newly diagnosed Parkinson's disease patients. We review roles of these drugs. The concept of neuroprotection in neurodegenerative disorders such as Parkinson's disease became popular in the mid 1980s and it is hoped that eventually therapy will be directed at slowing progression of the disease. A great deal more work needs to be done before a suitable agent is identified as being neuroprotective. Potential neuroprotective agents are reviewed. Surgical therapies for Parkinson's disease consisting of various forms of lesion surgery as well as stimulation procedures are reviewed. Complications of drug therapy include motor problems such as motor response fluctuations, as well as psychiatric complications including levodopa-induced psychosis. Atypical neuroleptic agents and ECT for psychiatric syndromes associated with Parkinson's disease are discussed. Algorithms for the management of early disease as well as the management of psychosis in Parkinson's disease are included. Treatment options for advanced disease are tabulated.

Many free nerve endings of small-diameter afferents (A-delta or C nerve fibres) respond to craniofacial noxious stimuli and a number of neurochemicals are involved in their activation or sensitization. The small-diameter nociceptive afferents project to the trigeminal (V) brainstem complex where they can excite nociceptive neurones that have been categorized as either nociceptive-specific (NS) or wide dynamic range (WDR). These neurones project to other brainstem regions or to the contralateral thalamus. The lateral and medial thalamus contain NS and WDR neurones which have properties and connections with the overlying cerebral cortex or other thalamic regions indicative of a role for most of them in the sensory-discriminative, affective or other dimensions of pain. Some of the V brainstem NS and WDR neurones respond exclusively to cutaneous sensory inputs and have features indicating their involvement in acute superficial craniofacial pain. Many of the neurones, however, receive convergent inputs from afferents supplying other craniofacial tissues (e.g. cerebrovascular, muscle) as well as skin, and are likely involved in deep pain, as well as spread and referral that is typically seen in headache and several craniofacial pain conditions involving deep tissues. Convergence may also be an important factor underlying the neuroplastic changes in V neuronal properties that may occur with peripheral injury or inflammation. These changes include a prolonged enhancement of the cutaneous as well as deep afferent inputs to most NS and WDR neurones and expansion of their cutaneous or deep mechanoreceptive field and increased EMG activity in the jaw musculature. They involve NMDA, non-NMDA and opioid neurochemical mechanisms within peripheral tissues as well as within the CNS. Such modulatory effects on brainstem neuronal properties reflect the functional plasticity of the central V system, and may be involved in the development of headache and other conditions that manifest craniofacial pain.

Parkinson's disease is a readily recognized clinical syndrome, characterized by resting tremor, rigidity, bradykinesia and loss of postural reflexes. The introduction of levodopa transformed our management of this disease. As our experience has increased the long term side effects of levodopa have become more apparent. Levodopa complications comprise: wearing off, motor fluctuations, and psychiatric complications. The complexity of these clinical phenomena has been worked out with time and is now well-recognized. A number of management strategies can ameliorate these long-term complications. This article reviews the current management of late-stage Parkinson's disease.

While dopamine agonists are still traditionally used as adjunct medications to improve performance and smooth out motor response complications in advanced levodopa-treated Parkinson's disease, they are increasingly used in monotherapy or early in combination with levodopa particularly in patients under 65 years of age. Long-term studies using bromocriptine showed efficacy in lowering the cumulative levodopa dose and reducing the early incidence of levodopa-related motor response complications. New dopamine agonists have recently shown efficacy as adjunct medications in short-term trials. While we now have more options to fit our individual patients' needs and tolerance, it is important to view the new agonists in the light of the results obtained with ergot derivatives. In this article, the rationale for use and efficacy profile of the ergolines are briefly reviewed.