Cognitive, Neurological, and Behavioral Features in Adults With KCNJ11 Neonatal Diabetes.

OBJECTIVE: Central nervous system (CNS) features in children with permanent neonatal diabetes (PNDM) due to KCNJ11 mutations have a major impact on affected families. Sulfonylurea therapy achieves outstanding metabolic control but only partial improvement in CNS features. The effects of KCNJ11 mutations on the adult brain and their functional impact are not well understood. We aimed to characterize the CNS features in adults with KCNJ11 PNDM compared with adults with INS PNDM. RESEARCH DESIGN AND METHODS: Adults with PNDM due to KCNJ11 mutations (n = 8) or INS mutations (n = 4) underwent a neurological examination and completed standardized neuropsychological tests/questionnaires about development/behavior. Four individuals in each group underwent a brain MRI scan. Test scores were converted to Z scores using normative data, and outcomes were compared between groups. RESULTS: In individuals with KCNJ11 mutations, neurological examination was abnormal in seven of eight; predominant features were subtle deficits in coordination/motor sequencing. All had delayed developmental milestones and/or required learning support/special schooling. Half had features and/or a clinical diagnosis of autism spectrum disorder. KCNJ11 mutations were also associated with impaired attention, working memory, and perceptual reasoning and reduced intelligence quotient (IQ) (median IQ KCNJ11 vs. INS mutations 76 vs. 111, respectively; P = 0.02). However, no structural brain abnormalities were noted on MRI. The severity of these features was related to the specific mutation, and they were absent in individuals with INS mutations. CONCLUSIONS: KCNJ11 PNDM is associated with specific CNS features that are not due to long-standing diabetes, persist into adulthood despite sulfonylurea therapy, and represent the major burden from KCNJ11 mutations.

Clinical and methodological confounders in assessing the cerebellar cognitive affective syndrome in adult patients with posterior fossa tumours.

The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.

Ironing out the rough spots--cognitive impairment in haemochromatosis.

A man in his late 40s, referred by his general practitioner (GP) to a psychology-led pain management programme, made a subjective and spontaneous report of cognitive impairment. He further mentioned a ten year history of erectile dysfunction, joint pain, occasional nausea and excessive fatigue. He underwent cognitive assessment. Advised to return to his GP to seek further investigation, he was ultimately subsequently diagnosed with haemochromatosis and began radical therapeutic venesection. Repeat cognitive assessment, a year later and following stabilisation of the condition, found improvement on some cognitive measures. Subjective report was of vastly improved cognitive function.

Loss of imagery phenomenology with intact visuo-spatial task performance: a case of 'blind imagination'.

The capacity for imagery, enabling us to visualise absent items and events, is a ubiquitous feature of our experience. This paper describes the case of a patient, MX, who abruptly lost the ability to generate visual images. He rated himself as experiencing almost no imagery on standard questionnaires, yet performed normally on standard tests of perception, visual imagery and visual memory. These unexpected findings were explored using functional MRI scanning (fMRI). Activation patterns while viewing famous faces were not significantly different between MX and controls, including expected activity in the fusiform gyrus. However, during attempted imagery, activation in MX's brain was significantly reduced in a network of posterior regions while activity in frontal regions was increased compared to controls. These findings are interpreted as suggesting that MX adopted a different cognitive strategy from controls when performing the imagery task. Evidence from experimental tasks thought to rely on mental imagery, such as the Brooks' matrices and mental rotation, support this interpretation. Taken together, these results indicate that successful performance in visual imagery and visual memory tasks can be dissociated from the phenomenal experience of visual imagery.

Cerebral emboli and cognitive function after intramedullary fracture fixation.

INTRODUCTION: Cerebral emboli have been detected during intramedullary orthopaedic procedures. The quantity of emboli produced and their clinical effects are currently not known. This study aimed to quantify the intra-operative cerebral embolic load using transcranial Doppler ultrasound during the intramedullary stabilisation of femoral and tibial diaphyseal fractures. Clinical cognitive function was also assessed after surgery and any relationship to the cerebral embolic load determined. PATIENTS AND METHODS: Prospective cohort study of 20 patients with femoral or tibial diaphyseal fractures treated with reamed intramedullary nailing. The intra-operative cerebral embolic load was measured using transcranial Doppler ultrasound of the middle meningeal artery. Cognitive function was assessed 3 days after surgery using a range of validated neuropsychological tests. The cognitive results were compared to predicted scores matched for age and intelligence quotient as is the standard method of cognitive assessment after trauma. RESULTS: Four patients had detectable cerebral emboli with counts of only 2, 3, 3, and 9 respectively. A significantly poorer than predicted cognitive score occurred in immediate and delayed memory recall tests. However there was no significant difference in any cognitive function score between those patients who had detectable cerebral emboli and those who did not. DISCUSSION: Small numbers of cerebral emboli were detected during intramedullary stabilisation of lower limb long bone fractures but with no apparent cognitive effect. This poor correlation is similar to recent studies performed on arthroplasty patients and also conforms to the extensive cardiac surgery literature which would indicate that such low levels of systemic embolisation are unlikely to consistently produce cerebral clinical effects.