A disease,disorder, illness or condition: How to label epilepsy?

The International League Against Epilepsy (ILAE) is an important source of guidance for health professionals when it comes to epilepsy. Their latest recommendation that epilepsy should no longer be called a “disorder,” but a “disease” has though caused controversy. The ILAE contends the change will improve epilepsy's image. Some clinicians and other organizations fear the change may not though be accepted by patients as in common parlance “disease” can be associated with “contagiousness”/”infection.” To allow practicing clinicians to make informed judgements about what language they use, we completed the first study to assess the preferences of those with epilepsy and significant others and explore if any of their characteristics were associated with preference. Via epilepsy interest groups and associations in England, Wales, Scotland and the Republic of Ireland, 971 patients and significant others were surveyed. Participants identified which of four labels for epilepsy (“disorder,” “illness,” “disease,” “condition”) they favoured and rated each using a Likert‐scale. Patients’ median age was 39; 69% had experienced seizures in the prior year. “Condition” was favoured by most patients (74.3%) and significant others (71.2%). Only 2.2% of patients and 1.2% of significant others chose “disease”; it received a median Likert‐rating indicating “strongly dislike.” Multinomial logistic regression found it was not possible to reliably distinguish between participants favouring the different terms on the basis of demographics. The ILAE's position is at odds with what most patients and carers want and we discuss the implications of this.     

Kennedy's disease: a triplet repeat disorder or a motor neuron disease?

Two definite genetic causes of adult motor neuron degeneration have been identified to date: CAG repeat expansion in the androgen receptor gene in Kennedy's disease and point mutations in the SOD1 gene, encoding the enzyme, Cu/Zn superoxide dismutase, in some familial forms of amyotrophic lateral sclerosis. Although both have unrelated genetic causes, Kennedy's disease and SOD1-linked amyotrophic lateral sclerosis share several pathogenic features. First, expanded androgen receptor and mutant Cu/Zn superoxide dismutase have a propensity to aggregate into insoluble complexes and form inclusion bodies in affected neurons. Deposits of mutant proteins could be detrimental to neuronal viability by interfering with the normal housekeeping functions of chaperones and of the ubiquitin/proteasome system. Secondly, cytoskeletal function may be impaired in both diseases as decreased transactivational activity of expanded androgen receptor may cause an abnormal pattern of tubulin expression in motor neurons in Kennedy's disease and disruption of neurofilament organisation is a hallmark of amyotrophic lateral sclerosis. The concept of activation of overlapping cell death cascades by two distinct genetic defects could help elucidating downstream pathogenic processes and may provide novel targets for pharmacological intervention or gene therapy for the treatment of motor neuron disorders.     

Kennedy’s disease: a triplet repeat disorder or a motor neuron disease?

Two definite genetic causes of adult motor neuron degeneration have been identified to date: CAG repeat expansion in the androgen receptor gene in Kennedy’s disease and point mutations in the SOD1 gene, encoding the enzyme, Cu/Zn superoxide dismutase, in some familial forms of amyotrophic lateral sclerosis. Although both have unrelated genetic causes, Kennedy’s disease and SOD1-linked amyotrophic lateral sclerosis share several pathogenic features. First, expanded androgen receptor and mutant Cu/Zn superoxide dismutase have a propensity to aggregate into insoluble complexes and form inclusion bodies in affected neurons. Deposits of mutant proteins could be detrimental to neuronal viability by interfering with the normal housekeeping functions of chaperones and of the ubiquitin/proteasome system. Secondly, cytoskeletal function may be impaired in both diseases as decreased transactivational activity of expanded androgen receptor may cause an abnormal pattern of tubulin expression in motor neurons in Kennedy’s disease and disruption of neurofilament organisation is a hallmark of amyotrophic lateral sclerosis. The concept of activation of overlapping cell death cascades by two distinct genetic defects could help elucidating downstream pathogenic processes and may provide novel targets for pharmacological intervention or gene therapy for the treatment of motor neuron disorders.     

Epilepsy or paroxysmal kinesigenic choreoathetosis?

Epileptic seizures induced by sudden movement and paroxysmal kinesigenic choreoathetosis (PKC) have often been confused in the past, owing to the close similarity of the attacks, the equally good response to anticonvulsants, and the frequent occurrence of epilepsy and PKC in the same family, or even in the same patient. The pathophysiology of PKC is still unclear and its relationship with epilepsy open to discussion. The sparing of consciousness and the lack of postictal phenomena are constant features of PKC, thus differentiating this syndrome from epilepsy. We report the case of an 8-year-old boy with frequent brief tonic attacks, without loss of consciousness, triggered by sudden movement. The neurologic examination, EEG and MRI did not help to differentiate between epilepsy and PKC. Only the occurrence of a longer seizure with clouding of consciousness and the recording of the postictal abnormalities on the EEG supported a diagnosis of reflex epilepsy induced by movement.     

Schizoaffective disorder: a form of schizophrenia or affective disorder?

BACKGROUND: The diagnostic status of schizoaffective disorder continues to be controversial. Researchers have proposed that schizoaffective disorder represents a variant of schizophrenia or affective disorder, a combination of the 2, or an intermediate condition along a continuum between schizophrenia and affective disorder. METHOD: We compared outpatients aged 45 to 77 years with DSM-III-R diagnosis of schizoaffective disorder (N = 29), schizophrenia (N = 154), or nonpsychotic mood disorder (N = 27) on standardized rating scales of psychopathology and a comprehensive neuropsychological test battery. A discriminant function analysis was used to classify the schizoaffective patients based on their neuropsychological profiles as being similar either to schizophrenia patients or to those with nonpsychotic mood disorder. RESULTS: The schizoaffective and schizophrenia patients had more severe dyskinesia, had a weaker family history of mood disorder, had been hospitalized for psychiatric reasons more frequently, were more likely to be prescribed neuroleptic and anticholinergic medication, and had somewhat less severe depressive symptoms than the mood disorder patients. The schizophrenia patients had more severe positive symptoms than the schizoaffective and mood disorder patients. The neuropsychological performances of the 2 psychosis groups were more impaired than those of the nonpsychotic mood disorder patients. Finally, on the basis of a discriminant function analysis, the schizoaffective patients were more likely to be classified as having schizophrenia than a mood disorder. CONCLUSION: These findings suggest that schizoaffective disorder may represent a variant of schizophrenia in clinical symptom profiles and cognitive impairment.     

CBCL-pediatric bipolar disorder phenotype: severe ADHD or bipolar disorder?

Summary Background. In children with pediatric bipolar disorder (PBD), a consistent pattern of elevations in hyperactivity, depression/anxiety, and aggression has been identified on the child behavior checklist (CBCL-PBD profile). The aim of the present study was to estimate the prevalence of the CBCL-PBD profile in a child psychiatric sample, and to determine ICD-10 diagnoses in CBCL-PBD patients. Methods. We studied a sample of 939 consecutively referred children and adolescents, aged 4–18 years. ICD-10 discharge diagnoses were established in consensus conferences. The CBCL 4–18 was completed by parents as part of the diagnostic routine. Results. A total of 62 subjects (6.6%; 95% CI=5.2–8.4) met criteria for the CBCL-PBD phenotype. More than 75% of CBCL-PBD subjects were clinically diagnosed with disruptive behavior disorders (ADHD, ODD, and CD). Two patients (0.2% of the total sample) received a formal diagnosis of bipolar disorder, but did not show the CBCL-PBD phenotype. Conclusions. A considerable number of children in Germany are referred to psychiatric care with a mixed phenotype of aggression, anxiety, depression and attention problems. Our study demonstrated a comparable prevalence and similar clinical characteristics as reported from other countries using different diagnostic approaches. However, the CBCL-PBD phenotype does not correspond with clinical consensus diagnoses of bipolar disorder, but with severe disruptive behavior disorders. Correspondence: Martin Holtmann, Department of Child and Adolescent Psychiatry and Psychotherapy, J.W. Goethe-University, Deutschordenstrasse 50, 60528 Frankfurt/Main, Germany     

Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics

The cause of Alzheimer's disease (AD) is unknown. This gap in knowledge has created a stumbling block in the search for a genuinely effective treatment or cure for this dementia. This article summarises the arguments for a causal role for either amyloid deposition or cerebrovascular pathology as the primary trigger in the development of non-genetic AD. A bare-bones survey of the published research reveals no compelling evidence that amyloid deposition is neurotoxic in human beings or that it results in neurodegenerative changes involving synaptic, metabolic, or neuronal loss in human or transgenic-mouse brains. By contrast, the data supporting AD as a primary vascular disorder are more convincing. Findings suggesting a vascular cause of AD come from epidemiological, neuroimaging, pathological, pharmacotherapeutic, and clinical studies. The consensus of these studies indicates that chronic brain hypoperfusion is linked to AD risk factors, AD preclinical detection and pharmacotherapeutic action of AD symptoms.     

Benign Partial Epilepsy in Infancy: Myth or Reality?

PURPOSE: Benign partial epilepsy in infancy (BPEI) was first described by Watanabe in 1987. The aim of this study is to describe a series of infants from the United States to characterize this entity further. METHODS: Among patients with the diagnosis of epilepsy followed up at our institution between 2002 and 2004, those satisfying the criteria for BPEI were included in a retrospective study. RESULTS: Sixteen (10.2%) of 150 patients with new onset of epilepsy younger than 2 years were identified. The mean age at seizure onset was 8 months. Four (25%) infants had a family history of benign seizures. All infants were neurologically and developmentally normal at the onset of seizures. The seizures occurred in clusters in 75% of patients, predominantly in wakefulness. The initial manifestation was behavioral arrest with staring (69%) and apnea with cyanosis or pallor (37.5%). These symptoms were followed by deviation of eyes or head or both (56%), mild clonic movements (31%), or increased limb tone (35%). Secondary generalization was noticed in 37.5% of patients. All infants had normal interictal EEGs and brain MRIs. Ictal EEGs disclosed electrographic seizures in 50% of patients (temporal origin in 62% and central in 38%). Fifteen (94%) patients were treated with AEDs with good response. The mean duration of treatment was 12.4 months. The final developmental assessment of all patients was normal. CONCLUSIONS: We believe that BPEI exists as a unique entity and should be included in the differential diagnosis of epilepsies in infancy with partial origin.     

Epilepsy or seizure disorder? The effect of cultural and socioeconomic factors on self-reported prevalence

Self-reported epilepsy may be influenced by culture, knowledge, and beliefs. We screened 6420 residents of the District of Columbia (DC) for epilepsy to investigate whether socio-demographics were associated with whether they reported their diagnosis as epilepsy or as seizure disorder. Lifetime and active prevalence rates were 0.54% and 0.21%, respectively for ‘epilepsy’ and 1.30% and 0.70%, respectively for ‘seizure disorder’. Seizure disorder was reported significantly more often than epilepsy among blacks, females, respondents ≥ 50 years, those with lower level education, respondents who lived alone and in low income neighborhoods, and those who resided in DC for at least five years. Clinicians should assure that patients and caregivers understand that epilepsy is synonymous with seizure disorder and other culturally appropriate terms, in order to optimize compliance with treatment, disease management instructions, and utilization of other resources targeted at persons with epilepsy. Furthermore, education and awareness campaigns aimed at improving access-to-care, reducing stigma, and increasing awareness of adverse events, such as SUDEP, should include a more diverse definition of epilepsy in their messages.