Music and epilepsy: a critical review

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl's gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native-born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe.     

Depression in epilepsy: a critical review from a clinical perspective

Depression is a serious and frequent comorbidity of epilepsy and other neurological conditions. Here, we review recent studies on the relationship between epilepsy and depression with regard to diagnostic criteria, epidemiology, etiology and treatment. Depression in epilepsy can be described in the general framework of the diathesis-stress model: chronic stress exposure owing to the 'burden of epilepsy' and learned helplessness due to the threat of recurrent seizures as unpredictable aversive events represent psychological risk factors for the development of depression. Epilepsy-related factors (for example, focus site or side) have shown little effect on mood. Nonepileptic individuals who are adversely affected by seizures (for example, parents of pediatric patients with epilepsy, and patients with psychogenic nonepileptic seizures) show increased levels of depression, similar to patients with epilepsy. However, seizures, subclinical hypersynchronous neural discharges and some antiepileptic drugs may cause acute states of depressive mood or depression on a purely neurobiological basis. Antidepressant drugs and psychotherapy have shown moderate efficacy in the treatment of depression comorbidity, but randomized controlled trials in patients with epilepsy are lacking, especially for drugs.     

Geriatric epilepsy: a review.

After the turn of the century, the proportion of population over 60 years of age is expected to be over 20%. Recent epidemiologic studies show a higher incidence of new-onset epilepsy in the population over 60 years of age compared with preceding decades of life. The predominant seizure type in up to 80% of these new cases of epilepsy is simple and complex partial manifestation. This paper reviews the literature documenting the increased incidence of partial seizures in the aging population, explores the known etiologies of new-onset epilepsy, and uses five case vignettes presenting with complex partial symptomatology.     

Neuroimaging studies of the early stages of psychosis: a critical review.

Psychiatric imaging, in particular functional imaging techniques such as functional magnetic resonance imaging (fMRI) are potentially powerful tools to explore the neurophysiological basis of the early stages of psychosis. Despite this impressive growth, neuroimaging has yet to become an established as diagnostic instrument this area, partly as a result of significant heterogeneity across the findings from research studies. The present review aims to: (i) assess the determinants of inconsistencies in the results from neuroimaging studies of the early stages of psychosis; and (ii) suggest approaches for future imaging research in this field that may reduce methodological differences between studies.     

Tissue culture studies of demyelinating disease: a critical review

Tissue culture studies of human and experimental demyelinating diseases have demonstrated that sera from patients with multiple sclerosis reversibly demyelinate central nervous system cultures. Similar changes are evoked by sera from animals with experimental allergic encephalomyelitis induced by inoculation with whole central nervous system tissue but not by encephalitogenic myelin basic protein. Sera and buffy coat or lymph node cells from humans with idiopathic polyneuritis and animals with experimental allergic neuritis demyelinate cultures of peripheral nervous system tissue. While these studies have contributed to speculations about pathogenetic mechanisms of demyelinating diseases, including the role of both circulating antibodies and delayed hypersensitivity factors, a number of important questions remain unanswered. Among these are the identity of the antigens that evoke antimyelin antibodies and the precise relationship of serum or cellular antimyelin factors to the pathogenesis or clinical course of the demyelinating diseases. Further studies with this technique may provide more complete information about the role of immunological events in induction of disease.     

Mapping prodromal psychosis: a critical review of neuroimaging studies

The onset of schizophrenia is usually preceded by a prodromal phase characterized by functional decline and subtle prodromal symptoms, which include attenuated psychotic phenomena, cognitive deterioration and a decline in socio-occupational function. Preventive interventions during this phase are of great interest because of the impressive clinical benefits. However, available psychopathological criteria employed to define a high risk state for psychosis have low validity and specificity. Consequently there is an urgent need of reliable neurocognitive markers linked to the pathophysiological mechanisms that underlie schizophrenia. Neuroimaging techniques have rapidly developed into a powerful tool in psychiatry as they provide an unprecedented opportunity for the investigation of brain structure and function. This review shows that neuroimaging studies of the prodromal phases of psychosis have the potentials to identify core structural and functional markers of an impending risk to psychosis and to clarify the dynamic changes underlying transition to psychosis and to address significant correlations between brain structure or function and prodromal psychopathology. Additionally, neurochemical methods can address the key role played by neurotransmitters such as dopamine and glutamate during the psychosis onset. To conclude, multimodal neuroimaging may ultimately clarify the neurobiology of the prodromal phases by the integration of functional, structural and neurochemical findings.     

Incidence and prevalence studies in epilepsy and their methodological problems: a review.

Epidemiological studies in epilepsy have a number of specific problems, discussed here with reference to the published literature. Case ascertainment may pose difficulties because of deficiencies in patients reporting and in the diagnosis of seizures, and inherent methodological problems; the classification of epilepsy is often arbitrary and definitions variable; unsuspected selection bias may markedly influence incidence and prevalence rates. The major published incidence and prevalence studies are reviewed and the factors influencing these rates discussed.     

Childhood trauma and psychotic disorders: a systematic, critical review of the evidence

There is controversy over whether childhood trauma (CT) is a causal factor in the development of psychosis. This review aims to identify and critically analyze the association between CT and psychotic disorders. Studies investigating CT and psychotic disorder were identified by searches of electronic databases and manual searches of references lists, and 46 studies were identified. Forty studies had no control group, only psychiatric control groups, or unmatched, nonpopulation control groups and thus had methodologies that were inadequate to determine the relationship between CT and psychosis. Six studies used appropriate control groups. Three studies found an association between CT and psychosis, 2 found potentially real associations that failed to reach statistical significance, and 1 found no association, tentatively suggesting a relationship between CT and psychotic disorders. Several methodological problems were found in the studies in the review, including the highest quality studies, which limit the strength of the conclusions that can be drawn from them. These were lack of statistical power, lack of attention to moderating or mediating variables, the way in which CT was measured, and the use of cross-sectional research designs. These problems, some of which may be unavoidable in CT research, suggest the need for new and innovative methodologies in the investigation of CT and psychosis. Directions for further research are explored.     

The prevalence of psychiatric disorders in epilepsy: a critical review of the evidence

Psychopathology has long been associated with epilepsy and should not be overlooked as it could exacerbate the epilepsy itself and impair the health-related quality of life of sufferers. A higher prevalence of psychiatric disorders has frequently been demonstrated amongst patients with epilepsy compared both with the general population and with individuals presenting neurological or non-neurological conditions. This review critically evaluates selected studies on the prevalence of psychiatric disorders in epilepsy patients compared with the general population and controls. Heterogeneity exists across the research methodologies, therefore further research, using less selected groups, should be undertaken to allow valid comparisons and the identification of more precise prevalence rates.     

A critical review of genetic studies of schizophrenia. II. Molecular genetic studies

Recent molecular genetic studies of schizophrenia have, until now, been unable to demonstrate any specific major gene for schizophrenia. On the contrary, linkage and association studies have yielded almost exclusively negative or contradictory results. Such studies have involved certain candidate genes, such as the genes, for dopamine receptors and other brain neurotransmitters. Some of these candidate genes have now actually been excluded as specific aetiological factors in schizophrenia. Similarly, studies searching for a major gene for susceptibility to schizophrenia involving the whole human genome or large parts of chromosomes have not yielded unambiguously positive results. However, the most recent empirical evidence suggests that many polygenes, acting together, could constitute a risk factor for schizophrenia. It is thus most probable that genetic susceptibility to schizophrenic psychoses is polygenic, and that their effects are dependent on interaction with physical and psychosocial environmental factors.     

Phenobarbital for the treatment of epilepsy in the 21st century: a critical review

Summary: Phenobarbital (PB) is the most widely used antiepileptic drug (AED) in the developing world and remains a popular choice in many industrialized countries. Meta-analyses of randomized controlled trials suggest that few differences in efficacy exist between PB and other established AEDs, but its possible deleterious cognitive and behavioral side effects remain a concern in the developed world. In contrast, high degrees of efficacy and tolerability in everyday clinical use have been demonstrated consistently in observational studies in developing countries. We propose that a pragmatic, comprehensive outcomes program be carried out, perhaps under the aegis of the Global Campaign Against Epilepsy, to optimize the conditions of the use of PB, so that more people around the world can benefit from this cost-effective medication and live more fulfilling lives.     

Childhood epilepsy in a German city

The incidence of epilepsy in children between 0 up to 8 years in the city of Kiel in Northern Germany was calculated. The study is based on a case documentation of the Kiel Epilepsy Center from 1957 to 1975. In this period 235 children were registered who were born in the years 1957 to 1966 and suffered from a single or recurrent epileptic seizures prior to their 9th birthday. Based upon the 37 691 children born in Kiel in the years 1957 to 1966, the mean cumulative risk for a single or recurrent epileptic seizures through the age of 8 is 6.23% (7.27% for boys, 5.12% for girls). Sixty percent of the children had their first seizure prior to the third birthday. The incidence rate for children below the age of 9 was 71.9/100.000 in 1965 and 72.4/100.000 in 1966. The maximum incidence rate was found in the first year of life (201.6).--The prevalence could only be estimated by summation of the cumulative incidence and was 4.5% in 1965. The clinical symptomatology was dominated by grand mal (68%), followed by partial seizures with complex (17%) and elementary symptomatology (16%), nonconvulsive generalized seizures (13%), infantile spasms (8%). Remarkably frequent is the benign epilepsy with centro-temporal sharp waves comprising 8% of the total group.     

Drug induced dyskinesia: a critical review.

Tardive dyskinesia (TD) has been reported to occur after the long term administration of neuroleptics. Its prevalence has been reported to vary from 0.5-56%. However, no clear relationship is established between a particular neuroleptic, its dosage and duration of administration and the diagnosis and occurrence of TD. Neuropathological investigations have not provided any definitive lessons. in addition, TD can be produced by a number of drugs of different chemical classes. Similarly, the evidence for dopaminergic hypersensitivity is equivocal. The only definitive feature seems to be an individual predisposition, the nature of which needs to be elucidated. Of course, basic to any future research into new insights regarding etiology, the fundamental problem of definition and identification based on the accepted definition are most essential. This solid foundation is necessary for the resolution of any conflicting results that may be reported in the future.     

Vagus nerve stimulation for epilepsy: a review.

Vagus nerve stimulation is an empirically based method for treatment of epilepsy by repeated stimulation of the left vagus nerve through implanted electrodes. Despite studies in animals and man, which show changes in brain electrophysiology, metabolism and neurochemistry, the mode of action remains unknown. Clinical testing has presented methodological challenges, as it is difficult to assess under double blind conditions a treatment which requires surgery and produces a sensation every time the stimulator comes on. This has nevertheless been successfully addressed in parallel design, controlled trials comparing high and low stimulation schedules. These have been performed in adults with medically intractable partial seizures, and demonstrated efficacy, safety and good tolerability. Efficacy, both in the controlled trials and in numerous reports arising from the considerable post-marketing experience is modest. Some 30% of patients achieve a 50% seizure reduction after 3 months of treatment, but this proportion progressively increases to about 50% after 18 months. Side-effects comprise: discomfort in the face or neck when the stimulator is activated, coughing, breathlessness on exertion and hoarseness of voice. All are related to intensity of stimulation and rapidly habituate in most subjects. In those patients who respond, a stimulus level can therefore generally be found which is acceptable to the subject. No indication other than refractory partial seizures in adults has been the subject of controlled trials, but post-marketing experience and uncontrolled reports indicate comparable efficacy and safety in a wide range of epilepsies, partial and generalized, idiopathic, cryptogenic, or symptomatic, in patients of all ages.     

Childhood epilepsy due to neurocysticercosis: a comparative study

PURPOSE: To assess the clinical profile of pediatric patients with epilepsy and neurocysticercosis (NC), and compare them with a group of pediatric patients with benign partial epilepsy to determine clinical differences, response to treatment, and prognosis. METHODS: We studied 28 patients (16 girls) with probable or definitive diagnosis of NC and epilepsy and 32 patients (16 girls) with partial benign epilepsy (BE). All patients had normal neurologic examination. We compared NC and BE patients looking for differences in demographics (age at first seizure, gender, family history); clinical presentation (type, frequency, duration, and total number of seizures, duration of epilepsy, status epilepticus, cluster, and postictal deficit); treatment [duration, number of antiepileptic drugs (AEDs), maximal dose, drug association, number of seizure-free patients, time to obtain control and recurrence after medication discontinuation]; complementary examinations (the first and the last EEG). RESULTS: The mean follow-up was 5.4 years for the 28 NC patients and 4.6 years for the 32 BE patients (p=0.98). We did not find statistical differences between NC and BE in gender, family history, types of seizures, frequency and length of seizures, previous status epilepticus, seizure clustering, and presence of postictal deficits. However, we found that NC compared with BE patients had significant longer AED treatment, more seizures after AED introduction, tried more AEDs and at maximal dose, and in 20%, required polytherapy. The recurrence rate in NC was 54.4% and this was not significantly associated with number of lesions and disease activity seen on CT scans or the presence of EEG abnormalities. CONCLUSIONS: NC presents with a mild form of epilepsy in terms of seizure severity; however, it is more challenging in regard to drug management and has a less favorable long-term prognosis in terms of seizure remission. The number of lesions or disease activity seen on computed tomography (CT) as well as EEG abnormalities have no prognostic value in childhood epilepsy due to NC.     

Childhood obsessive-compulsive disorder: a review

Obsessive-compulsive disorder (OCD) holds a particular interest for child psychiatrists because of the high proportion of cases with onset in childhood and adolescence. Over the last two decades, substantial progress has been made in describing OCD in children and adolescents and in developing and implementing effective treatments. In addition, research on the phenomenology, neurobiology, and psychopharmacology of OCD has led to its current conceptualization as a developmental neuropsychiatric disorder. In this article, the fourth in a series on OCD, the authors summarize the most recent data on the phenomenology, etiology, neurobiology, and treatment of OCD in children and adolescents.