CADASIL: neuropsychological findings in three generations of an affected family.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary brain disease with a variety of neurologic and psychiatric manifestations. We studied 3 members of a family who each had leukoencephalopathy on neuroimaging studies and a characteristic mutation for CADASIL in the notch 3 region of chromosome 19q12. In all 3 cases, neurobehavioral impairment dominated the clinical picture, and a pattern of psychiatric dysfunction heralding cognitive decline emerged. Neuropsychological evaluation revealed diverse deficits, but a profile of frontal lobe dysfunction, declarative memory impairment suggestive of a retrieval deficit, and relatively preserved language was evident. These cases provide a cross-sectional study of the evolution of CADASIL, and suggest that, as in other diseases characterized by white matter dementia, psychiatric dysfunction may occur initially, followed by pervasive cognitive dysfunction later in the course of the disease. CADASIL should be considered in young adults with unexplained leukoencephalopathy on neuroimaging studies, and in those with neurobehavioral dysfunction and a suggestive family history.     

Primary Progressive Aphasia in a Bilingual Woman

Multilingual aphasias are common because most people in the world know more than one language, but little is known of these syndromes except in patients who have had a stroke. We present a 76-year-old right-handed woman, fluent in English and Chinese, who developed anomia at age 70 and then progressed to aphasia. Functional neuroimaging disclosed mild left temporoparietal hypometabolism. Neurolinguistic testing was performed in both English and Chinese, representing a unique contribution to the literature. Results revealed conduction-like aphasia that was comparable in the two languages, although English was slightly better preserved. Primary progressive aphasia has disrupted 2 languages in a similar manner, suggesting their close neuroanatomic relationship in this case.     

Functional bases for a central serotonergic involvement in classic migraine: a speculative view

The r?le of serotonin (5-HT) in the cerebrovascular bed is the subject of the following review. Cerebral blood vessels are supplied with 5-HT-containing fibres which originate in the raphé nuclei in the brainstem. The activation of this system may result in a constriction of large arteries and a dilatation of arterioles. Intra-arterial administration of 5-HT causes reduction in cerebral blood flow and metabolism provided it bypasses the blood-brain barrier. The findings, marked changes in plasma levels of 5-HT and in cerebral blood flow during a classic migraine attack, are suggestive of an involvement of the 5-HT system.     

Neuroleptic medications inhibit complex I of the electron transport chain

Neuroleptic medications are prescribed to millions of patients, but their use is limited by potentially irreversible extrapyramidal side effects. Haloperidol shows striking structural similarities to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine, which produces parkinsonism apparently through inhibition of NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial electron transport chain. We now report that haloperidol chlorpromazine, and thiothixine inhibit complex I in vitro in rat brain mitochondria. Clozapine, an atypical antipsychotic reported to have little or no extrapyramidal toxicity, also inhibits complex I, but at a significantly higher concentration. Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson's disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.     

Delayed reduplicative paramnesia

A 25-year-old man with a remote history of closed head injury and left hemiparesis developed the false belief that his hospital was located in another city, close to his home. This delusion appeared more than 3 years after his injury, from which he had made a good recovery. No previous delusional or other psychotic thinking had occurred. Clinical and neuropsychological data supported the existence of right hemisphere and bifrontal pathology. This case illustrates that a specific delusional belief may arise in a patient with appropriate cerebral pathology years after the initial event.     

Cognition, MRS neurometabolites, and MRI volumetrics in non-neuropsychiatric systemic lupus erythematosus: preliminary data.

OBJECTIVE: To correlate cognitive dysfunction with structural and neurometabolic brain findings in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). BACKGROUND: Over 25% of non-NPSLE patients have cognitive dysfunction, but the cerebral basis of this observation is not well understood. METHOD: Seven patients with non-NPSLE and seven control subjects were given a series of neuropsychological tests and neuroimaging with magnetic resonance imaging and magnetic resonance spectroscopy. Analyses of cognitive function and structural and neurometabolic measures of the brain were performed. RESULTS: Compared with controls, the non-NPSLE patients were significantly impaired on a global cognitive impairment index (CII). No significant differences between the groups were found in choline/creatine (Ch/Cr), N-acetylaspartic acid/Cr, or hippocampal volumes. Ch/Cr was highly associated with CII across the sample. CONCLUSIONS: This is the first study to correlate cognitive impairment with an increase in Ch/Cr ratio among patients with SLE. These results, although preliminary, suggest that changes in cerebral white matter may be important in determining the subtle cognitive impairment that may occur in patients with SLE, even in the absence of neuropsychiatric symptoms.     

Concussion in sports. Guidelines for the prevention of catastrophic outcome

Concussion (defined as a traumatically induced alteration in mental status, not necessarily with loss of consciousness) is a common form of sports-related injury too often dismissed as trivial by physicians, athletic trainers, coaches, sports reporters, and athletes themselves. While head injuries can occur in virtually any form of athletic activity, they occur most frequently in contact sports, such as football, boxing, and martial arts competition, or from high-velocity collisions or falls in basketball, soccer, and ice hockey. The pathophysiology of concussion is less well understood than that of severe head injury, and it has received less attention as a result. We describe a high school football player who died of diffuse brain swelling after repeated concussions without loss of consciousness. Guidelines have been developed to reduce the risk of such serious catastrophic outcomes after concussion in sports.