Is late‐onset schizophrenia a subtype of schizophrenia?

Vahia IV, Palmer BW, Depp C, Fellows I, Golshan S, Kraemer HC, Jeste DV. Is late‐onset schizophrenia a subtype of schizophrenia? Objective: To determine whether late‐onset schizophrenia (LOS, onset after age 40) should be considered a distinct subtype of schizophrenia. Method: Participants included 359 normal comparison subjects (NCs) and 854 schizophrenia out‐patients age >40 (110 LOS, 744 early‐onset schizophrenia or EOS). Assessments included standardized measures of psychopathology, neurocognition, and functioning. Results: Early‐onset schizophrenia and LOS groups differed from NCs on all measures of psychopathology and functioning, and most cognitive tests. Early‐onset schizophrenia and LOS groups had similar education, severity of depressive, negative, and deficit symptoms, crystallized knowledge, and auditory working memory, but LOS patients included more women and married individuals, had less severe positive symptoms and general psychopathology, and better processing speed, abstraction, verbal memory, and everyday functioning, and were on lower antipsychotic doses. Most EOS–LOS differences remained significant after adjusting for age, gender, severity of negative or deficit symptoms, and duration of illness. Conclusion: Late‐onset schizophrenia should be considered a subtype of schizophrenia.     

Does cannabis onset trigger cocaine onset? A case‐crossover approach

Psychiatric researchers tend to select the discordant co-twin design when they seek to hold constant genetic influence while estimating exposure-associated disease risk. The epidemiologic case-crossover research design developed for the past two decades represents a viable alternative, not often seen in psychiatric studies. Here, we turn to the epidemiologic case-crossover approach to examine the idea that cannabis onset is a proximal trigger for cocaine use, with the power of "subject-as-own-control" research used to hold constant antecedent characteristics of the individual drug user, including genetic influence and other traits experienced up to the time of the observed hazard and control intervals. Data are from newly incident cocaine users identified in the 2002-2006 US National Surveys on Drug Use and Health. Among these cocaine users, 48 had both cannabis onset and cocaine onset in the same month-long hazard interval; the expected value is 30 users, based on the control interval we had pre-specified for case-crossover estimation (estimated relative risk, RR = 1.6; exact mid-p = 0.042). Within the framework of a subject-as-own-control design, the evidence is consistent with the hypothesis that cannabis onset is a proximal trigger for cocaine use, with genetic influences (and many environmental conditions and processes) held constant. Limitations are noted and implications are discussed.     

Does education moderate neuropsychological impairment in late‐life depression?

OBJECTIVE: The increased resistance of better-educated individuals to the cognitive effects of neuropathology has been conceptualized as reflecting brain reserve. This study examined whether educational level influences the degree of neuropsychological impairment associated with late-life depression. METHODS: The neuropsychological performances of 115 older depressed patients and of 44 comparison subjects of similar age and education were compared as a function of educational level. RESULTS: While depressed patients performed worse than comparison subjects on all the measures, the severity of this impairment (with respect to comparison subjects) did not differ with the educational level of the patients. CONCLUSIONS: Brain reserve, as indexed by the patients' level of education, does not mitigate the cognitive decrements associated with late-life depression.     

How long do new‐onset seizures in children last?

Although there are data on the duration of seizures in patients with refractory epilepsy, little is known about the duration of seizures in nonrefractory epilepsy populations. In a prospective study, seizure duration was determined in 407 children with a first unprovoked seizure using a structured interview and review of medical and ambulance records. Analysis focused on the distribution of seizure duration and on the conditional probability that a seizure would stop once it had already lasted for a specified time. Seizures lasted > or = 5 minutes in 50% of cases, > or = 10 minutes in 29%, > or = 20 minutes in 16%, and > or = 30 minutes in 12%. Seizure duration data were best fit as the sum of two exponential distributions, one with a mean of 3.6 minutes accounting for 76% of cases and the other with a mean of 31 minutes accounting for 24% of cases. The longer a seizure lasted, the less likely it was to stop within the next few minutes. In the 182 children with 2 or more seizures, the durations of the first and second seizures were highly correlated (r = 0.395, p < 0.0001). We conclude that the distribution of seizure duration in children with a first unprovoked seizure differs markedly from that observed in patients with refractory epilepsy. A subgroup of patients are predisposed to prolonged seizures. The data suggest that, once a seizure lasts for more than 5-10 minutes, it is unlikely to stop spontaneously within the next few minutes, and intervention is therefore indicated. These findings also support the continued use of the current definition of status epilepticus as a seizure lasting for 30 minutes or longer for epidemiologic studies.     

Frontal lobe syndrome or adolescent‐onset schizophrenia? A case report

OBJECTIVE: To highlight the difficulties that abound in making a clinical distinction between early-onset schizophrenia (EOS) and juvenile frontal dementia early in the course of illness. METHOD: Clinical information and data from investigations in single case was collated and reviewed. RESULTS: A 15-year-old girl was admitted to our psychiatric unit because of cognitive decline and formal thought disorder with echopraxia, echolalia and palilalia, and a lack of flexibility in the use of cognitive and motor strategies that culminated in psychosis. A single photon emission computerized tomography scan showed marked frontal lobe hypoperfusion; however, on proton spectroscopy there was no differential in N-acetyl aspartate levels. CONCLUSION: Hypofrontality in EOS is well established and the association of frontal functional alterations, neuropsychological impairment and psychotic symptomatology is suggestive of frontal lobe prodrome that precedes the onset of psychosis.     

Good outcome in adult‐onset Rasmussen's encephalitis syndrome: is recovery possible?

A healthy 29‐year‐old man suffered from adult‐onset epilepsy, characterized by polymorphic progressive seizures resistant to AEDs, leading to unilateral cortical deficits and atrophy of the left hemisphere. The disorder satisfied the clinical, EEG, and imaging criteria for a diagnosis of Rasmussen's encephalitis. During the acute phase of the disease, intrathecal synthesis of specific anti‐CMV IgG was identified. This case was characterized by a very mild course and remission of seizures following a treatment with high‐dose intravenous polyvalent immunoglobulins containing a high anti‐CMV titre. The patient remained symptomless for more than 15 years from clinical onset and more than eight years after the discontinuation of immunological therapy. In agreement with a recent report, this case confirms that adult‐onset Rasmussen's encephalitis syndrome may occur with a very mild clinical picture and persistent remission. In this case, the specific index for intrathecal production of anti‐CMV antibodies suggested possible CMV involvement, indicating specific immuno‐therapy as a treatment choice.     

Cryptogenic Late‐onset Epileptic Spasms: An Overlooked Syndrome of Early Childhood?

PURPOSE: Few reports detailing late-onset epileptic spasms have been published. To determine whether this condition merely represents a late variant of classic West syndrome or exhibits specific features distinct from the latter and related to a later stage of brain maturation, we analyzed the whole population with this specific seizure type, excluding symptomatic cases to avoid the effect of brain lesion. METHODS: We reviewed the files of the 56 children evaluated for epileptic spasms in clusters having begun at age 12 months or later and analyzed clinical and video-EEG data of the 22 patients (4-17 years; mean, 8.5 years) without obvious cause. RESULTS: Interictal EEG did not show classic hypsarrhythmia. A temporal or temporofrontal slow wave and/or spike focus could be identified in all cases. Twelve children showed spasms with a tonic component. Ictal EEG revealed generalized high-voltage slow wave followed by diffuse voltage attenuation with superimposed fast activity. All children also exhibited other types of recorded seizures consisting of bursts of spike-waves with temporofrontal predominance, reminiscent of "atypical absences." In contrast with the occurrence of tonic components within a cluster of spasms, no tonic seizure stricto sensu was recorded or reported by the caregivers. In 10 children, treatment (two vigabatrin, seven hydrocortisone, one adrenocorticotropic hormone) achieved complete cessation of seizures and disappearance of focal EEG anomalies, but spasms persisted in 12 children. CONCLUSIONS: The cryptogenic group in our series without recognized cause and temporal or temporofrontal EEG anomalies seems to represent a type of epileptic encephalopathy intermediary between West and Lennox-Gastaut syndromes, in terms of seizure types and interictal EEG, and could correspond to dysfunction of the maturation process of the temporal lobe, possibly due to an undisclosed lesion.     

What is ‘early onset dementia’?

There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelarted onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a ‘presenile dementia’. Since the 1980s, ‘senile dementia of Alzheimer type’ (SDAT) and ‘Alzheimer's disease’ have been considered to belong to the same pathological entity and both are now known as ‘dementia of Alzheimer's type (DAT)’ or merely ‘Alzheimer's disease’. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.