The modern antiretroviral treatment of human immunodeficiency virus (HIV-1) infection has considerably lowered the incidence of opportunistic infections. With the exception of the most severe dementia manifestations, the incidence and prevalence of HIV-associated neurocognitive disorders (HAND) have not decreased, and HAND continues to be relevant in daily clinical practice. Now, HAND occurs in earlier stages of HIV infection, and the clinical course differs from that before the widespread use of combination antiretroviral treatment (cART). The predominant clinical feature is a subcortical dementia with deficits in the domains concentration, attention, and memory. Motor signs such as gait disturbance and impaired manual dexterity have become less prominent. Prior to the advent of cART, the cerebral dysfunction could at least partially be explained by the viral load and by virus-associated histopathological findings. In subjects where cART has led to undetectable or at least very low viral load, the pathogenic virus–brain interaction is less direct, and an array of poorly understood immunological and probably toxic phenomena are discussed. This paper gives an overview of the current concepts in the field of HAND and provides suggestions for the diagnostic and therapeutic management.

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Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND.

Glycogen storage diseases are important causes of myopathy and cardiomyopathy. We describe 10 patients from 8 families with childhood or juvenile onset of myopathy, 8 of whom also had rapidly progressive cardiomyopathy, requiring heart transplant in 4. The patients were homozygous or compound heterozygous for missense or truncating mutations in RBCK1, which encodes for a ubiquitin ligase, and had extensive polyglucosan accumulation in skeletal muscle and in the heart in cases of cardiomyopathy. We conclude that RBCK1 deficiency is a frequent cause of polyglucosan storage myopathy associated with progressive muscle weakness and cardiomyopathy. Ann Neurol 2013;74:914–919

The study compares 5 auditory event-related potential (ERP) components (P1 to P3) after 3 tones differing in pitch and rarity, and contrasts the mismatch negativity (MMN) between them in 12 children with attention-deficit hyperactivity disorder (ADHD; mean 10.2 years of age), 12 healthy controls pairwise matched for age (controls), and 10 with Chronic Tic or Tourette Syndrome (TS). Topographic recordings were derived from 19 scalp electrodes. Four major effects are reported. (a) Shorter latencies in ADHD patients were evident as early as 100 ms. (b) Both ADHD and TS groups showed very large P2 components where the maxima were shifted anteriorly. The differences in the later potentials were of a topographical nature. (c) Frontal MMN was non-significantly larger in the ADHD group but normalized data showed a left rather than a right frontal bias as in control subjects. Maxima for TS were usually posterior. (d) ADHD patients did not show the usual right-biased P3 asymmetry nor the frontal versus parietal P3 latency difference. From these results it is suggested that ADHD patients process perceptual information faster from an early stage (N1). Further, along with the TS group, ADHD patients showed an unusually marked inhibitory phase in processing (P2), interpreted as a reduction of the normal controls on further processing. Later indices of stimulus processing (N2-P3) showed a frontal impairment in TS and a right hemisphere impairment in ADHD patients. These are interpreted in terms of the difficulties in sustaining attention experienced by both ADHD and TS patients.