Improving clinical cognitive testing: report of the AAN Behavioral Neurology Section Workgroup.

OBJECTIVE: To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. METHODS: Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. RESULTS: Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. CONCLUSIONS: We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment.

Pelizaeus-Merzbacher syndrome: neurocognitive function in a family with carrier manifestations.

A Cajun kindred with Pelizaeus-Merzbacher disease was found to have a p.Q128X mutation in exon 3B of proteolipid protein 1 (PLP1). The affected males were globally delayed in development, nonambulatory, and severely dysarthric. The heterozygous females developed progressive gait disturbances and cognitive deterioration starting in the fourth decade of life. The average IQ (Stanford-Binet Intelligence Scale: 4th Edition (SBFE)) of the carrier females was 54.2, compared to the average IQ of 97.5 in nonaffected relatives. The X-inactivation ratios in the three carrier females were not markedly skewed (55:45, 70:30, and 85:15). The presence of neurological and cognitive deterioration in the three carriers deviates from the usual expectation that carrier expression only occurs in families when males are mildly affected.

Altered neurodevelopment associated with mutations of RSK2: a morphometric MRI study of Coffin-Lowry syndrome.

Coffin-Lowry syndrome (CLS) is a rare form of X-linked mental retardation caused by mutations of the RSK2 gene, associated with cognitive impairment and skeletal malformations. We conducted the first morphometric study of CLS brain morphology by comparing brain volumes from two CLS families with healthy controls. Individuals with CLS consistently showed markedly reduced total brain volume. Cerebellum and hippocampus volumes were particularly impacted by CLS and may be associated with specific interfamilial RSK2 mutations. We provide preliminary evidence that the magnitude of hippocampus volume deviation from that of controls may predict general cognitive outcome in CLS.

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene.

Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutations in the monocarboxylate transporter 8 gene (MCT8) have been found in each of the six families. One essential function of the protein encoded by this gene appears to be the transport of triiodothyronine into neurons. Abnormal transporter function is reflected in elevated free triiodothyronine and lowered free thyroxine levels in the blood. Infancy and childhood in the Allan-Herndon-Dudley syndrome are marked by hypotonia, weakness, reduced muscle mass, and delay of developmental milestones. Facial manifestations are not distinctive, but the face tends to be elongated with bifrontal narrowing, and the ears are often simply formed or cupped. Some patients have myopathic facies. Generalized weakness is manifested by excessive drooling, forward positioning of the head and neck, failure to ambulate independently, or ataxia in those who do ambulate. Speech is dysarthric or absent altogether. Hypotonia gives way in adult life to spasticity. The hands exhibit dystonic and athetoid posturing and fisting. Cognitive development is severely impaired. No major malformations occur, intrauterine growth is not impaired, and head circumference and genital development are usually normal. Behavior tends to be passive, with little evidence of aggressive or disruptive behavior. Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.

Prefrontal executive function syndromes in children.

"Executive function" is a term describing the processes required for conscious control of thought, emotion, and action that are central to the management of one's day-to-day life. Executive function is subserved by the prefrontal cortex and related subcortical structures. Disorders affecting the prefrontal cortex-subcortical system are numerous and heterogeneous, but contemporary research has begun to elucidate the mechanisms and consequences of dysfunction in various subsystems with increasing specificity. Prefrontal executive dysfunction results in impaired regulation of cognition, attention, behaviors, arousal, and emotion, all of which have serious and pervasive consequences for functioning across the life span. These executive function deficits are typically difficult to treat, ameliorate, or remediate and require sensitive handling by caretakers. Executive dysfunction can arise as a consequence of many different factors (metabolic, genetic, certain types of epilepsy, cerebral dysgenesis, prematurity, traumatic brain injury, hypoxia, and toxic exposure). The present review delineates the features of prefrontal executive function deficits in children and proposes a roadmap for their diagnosis, treatment, and management.

Attention-deficit hyperactivity disorder (ADHD).

Approaches to the diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) are undergoing a major change as a result of information from studies on the genetics of ADHD and the use of new neuroimaging technologies. Moreover, pharmacogenomics, although still in its infancy, will provide a basis for much more sophisticated treatment strategies for ADHD, particularly once more information is available about the genetics of ADHD. Even at this point in time, there is some pertinent information available that, although not ready for application in clinical settings, nonetheless provides a broader perspective for the clinician. In terms of etiology, ADHD is a neuropsychiatric disorder. There is a genetic basis in about 80% of the cases, involving a number of different genes, and in about 20% of the cases, ADHD is the result of an acquired insult to the brain. Some individuals likely have both genetic and acquired forms. Although medication works well in many cases of ADHD, optimal treatment of ADHD requires integrated medical and behavioral treatment. The family plays a crucial role in the management of children with ADHD. Because there is often a very high degree of comorbidity between ADHD and learning disabilities, teachers also have a great deal to contribute in the day-to-day management of these children. Early recognition and treatment prevent the development of more serious psychopathology in adolescence and adulthood.

Psychiatric implications of language disorders and learning disabilities: risks and management.

This article reviews the relationship between different learning disabilities, language disorders, and the psychiatric disorders that are commonly associated with learning disabilities and language disorder: attention-deficit hyperactivity disorder (ADHD), anxiety disorders, depression, and conduct or antisocial personality disorder. The complex associations between language disorders and specific learning disabilities--dyslexia, nonverbal learning disorder, dyscalculia--and the various psychiatric disorders are discussed. Clinical vignettes are presented to highlight the impact of these disorders on a child's social and psychological development and the importance of early recognition and treatment.