Integration of adult patients with phenylketonuria into professional life: long-term follow-up of 27 patients in a single centre in Switzerland

BACKGROUND Neonatal screening and treatment of phenylketonuria (PKU) prevent the development of neurocognitive impairment. The degree of dysfunction may be related to metabolic control and responsible for a hampered school career. METHODS This was a retrospective study from a single metabolic unit of a Swiss University Hospital. The time point of diagnosis and all Phenylalanin (Phe) concentrations during the follow-up were recorded. The primary outcome was integration into professional life defined as no professional studies versus accomplished apprenticeship versus high school diploma/university. Phe levels were correlated with professional outcome. The control group consisted of the patients' healthy parents and siblings. RESULTS A total of 27 patients (13 females, 14 males) were included in the study. The mean (SD) follow-up period was 25.1 (7.6) years. The control group consisted of 57 subjects. Overall, 23 patients were diagnosed by neonatal screening, and 4 patients were diagnosed later. All 4 were in the non-professional study group. Compared with the controls there were significantly more patients in the non-professional study group (26% vs 9%, p <0.05) and significantly less in the accomplished apprenticeship group (59% vs 82%; p <0.04). After exclusion of the patients with late diagnosis no significant differences were found with regard to the professional integration between patients and controls. Significant differences in Phe-levels between the three groups could be documented between 2-10 years of age with the highest levels in the non-professional study followed by the accomplished apprenticeship and the high school diploma group (p <0.01). CONCLUSION Patients who are diagnosed by neonatal screening and are consequently cared for are able to accomplish an apprenticeship or a high school diploma.

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

Psychosocial and neurocognitive performance after spontaneous nonaneurysmal subarachnoid hemorrhage related to the APOE-epsilon4 genotype: a prospective 5-year follow-up study

OBJECT: In this study, the authors prospectively evaluated long-term psychosocial and neurocognitive performance in patients suffering from nonaneurysmal, nontraumatic subarachnoid hemorrhage (SAH) and investigated the association between the APOE-epsilon4 genotype and outcome in these patients. METHODS: All patients admitted to the authors' institution between January 2001 and January 2003 with spontaneous nonaneurysmal SAH were prospectively examined (mean follow-up 59.8 months). The APOE genotype was determined in all patients by polymerase chain reaction from a blood sample. Of the 30 patients included in this study, 11 were carriers of the epsilon4 allele. RESULTS: All patients showed a good recovery and regained full independence with no persisting neurological deficits. The patients with the epsilon4 allele, however, scored significantly higher on the Beck Depression Inventory (22.1 +/- 6.3 vs 14.1 +/- 5.1). At follow-up, depression was more persistent in the group with the epsilon4 allele compared with the group that lacked the allele. This finding reached statistical significance (p < 0.05). Selective attention was impaired in all patients during the first year of follow-up, with an earlier recovery noted in the patients without the epsilon4 allele. Moreover, there was a tendency toward a linear relationship between the Beck Depression Inventory and the d2 Test of Attention. Two patients who carried the epsilon4 allele did not return to their employment even after 5 years. CONCLUSIONS: The findings in this study suggest that the APOE genotypes may be associated with the psychosocial and neurocognitive performance after spontaneous nonaneurysmal SAH, even in the absence of neurological impairment. Physicians should consider patient genotype in assessing the long-term consequences of nonaneurysmal SAH.

Childhood Trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indetured child laborers in old Age.

A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood.

Mild cognitive impairment in medical inpatients: the mini-mental state examination is a promising screening tool

AIM: To assess the prevalence of mild cognitive impairment (MCI) in medical inpatients aged 55-85 years without known cognitive deficits, and how often ward physicians mentioned MCI in their discharge notes. Moreover, we aimed to identify variables associated with MCI and to assess the sensitivity and specificity of the Mini-Mental State Examination (MMSE) for MCI. METHODS: Two neuropsychologists administered a 60-min battery of validated tests to evaluate different cognitive domains. The diagnosis of MCI was based on a prespecified algorithm. The sensitivity and specificity of the MMSE for MCI were calculated. RESULTS: Fifteen patients showed a normal cognitive profile (21.4%), while 55 patients (78.6%) showed MCI. Ward physicians, blinded to the results of the neuropsychological evaluation, did not mention MCI in their discharge notes of any of the evaluated patients. The only variable independently associated with MCI was the MMSE. A MMSE score of < or =28 showed a sensitivity of 85.5% and a specificity of 66.7% for MCI. CONCLUSION: MCI is frequent albeit overlooked in elderly medical inpatients without previously known cognitive deficits. In view of therapies preventing the progression of MCI to dementia, MCI screening will be crucial. The MMSE represents a promising screening tool for MCI in medical inpatients.

Bilateral impairment of concurrent saccade programming in hemispatial neglect

When healthy observers make a saccade that is erroneously directed toward a distracter stimulus, they often produce a corrective saccade within 100ms after the end of the primary saccade. Such short inter-saccadic intervals indicate that programming of the secondary saccade has been initiated prior to the execution of the primary saccade and hence that the two saccades have been programmed concurrently. Here we show that concurrent saccade programming is bilaterally impaired in left spatial neglect, a strongly lateralized disorder of visual attention resulting from extensive right cerebral damage. Neglect patients were asked to make saccades to targets presented left or right of fixation while disregarding a distracter presented in the opposite hemifield. We examined those experimental trials on which participants first made a saccade to the distracter, followed by a secondary (corrective) saccade to the target. Compared to healthy and right-hemisphere damaged control participants the proportion of secondary saccades directing gaze to the target instead of bringing it even closer to the distracter was bilaterally reduced in neglect patients. In addition, the characteristic reduction of secondary saccade latency observed in both control groups was absent in neglect patients, whether the secondary saccade was directed to the left or right hemifield. This pattern is consistent with a severe, bilateral impairment of concurrent saccade programming in left spatial neglect.

Incidence and predictors of atrioventricular conduction impairment after transcatheter aortic valve implantation

Atrioventricular (AV) conduction impairment is well described after surgical aortic valve replacement, but little is known in patients undergoing transcatheter aortic valve implantation (TAVI). We assessed AV conduction and need for a permanent pacemaker in patients undergoing TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards Sapien Valve (ESV). Sixty-seven patients without pre-existing permanent pacemaker were included in the study. Forty-one patients (61%) and 26 patients (39%) underwent successful TAVI with the MCRS and ESV, respectively. Complete AV block occurred in 15 patients (22%), second-degree AV block in 4 (6%), and new left bundle branch block in 15 (22%), respectively. A permanent pacemaker was implanted in 23 patients (34%). Overall PR interval and QRS width increased significantly after the procedure (p <0.001 for the 2 comparisons). Implantation of the MCRS compared to the ESV resulted in a trend toward a higher rate of new left bundle branch block and complete AV block (29% vs 12%, p = 0.09 for the 2 comparisons). During follow-up, complete AV block resolved in 64% of patients. In multivariable regression analysis pre-existing right bundle branch block was the only independent predictor of complete AV block after TAVI (relative risk 7.3, 95% confidence interval 2.4 to 22.2). In conclusion, TAVI is associated with impairment of AV conduction in a considerable portion of patients, patients with pre-existing right bundle branch block are at increased risk of complete AV block, and complete AV block resolves over time in most patients.

Long-Term outcome in patients with mild traumatic brain injury: A prospective observational study

Mild traumatic brain injury (MTBI) is common; up to 37% of adult men have a history of MTBI. Complaints after MTBI are persistent headaches, memory impairment, depressive mood disorders, and disability. The reported short- and long-term outcomes of patients with MTBI have been inconsistent. We have now investigated long-term clinical and neurocognitive outcomes in patients with MTBI (at admission, and after 1 and 10 years).

Trunk sway in mildly disabled multiple sclerosis patients with and without balance impairment

Multiple sclerosis (MS) causes a broad range of neurological symptoms. Most common is poor balance control. However, knowledge of deficient balance control in mildly affected MS patients who are complaining of balance impairment but have normal clinical balance tests (CBT) is limited. This knowledge might provide insights into the normal and pathophysiological mechanisms underlying stance and gait. We analysed differences in trunk sway between mildly disabled MS patients with and without subjective balance impairment (SBI), all with normal CBT. The sway was measured for a battery of stance and gait balance tests (static and dynamic posturography) and compared to that of age- and sex-matched healthy subjects. Eight of 21 patients (38%) with an Expanded Disability Status Scale of 1.0-3.0 complained of SBI during daily activities. For standing on both legs with eyes closed on a normal and on a foam surface, patients in the no SBI group showed significant differences in the range of trunk roll (lateral) sway angle and velocity, compared to normal persons. Patients in the SBI group had significantly greater lateral sway than the no SBI group, and sway was also greater than normal in the pitch (anterior-posterior) direction. Sway for one-legged stance on foam was also greater in the SBI group compared to the no SBI and normal groups. We found a specific laterally directed impairment of balance in all patients, consistent with a deficit in proprioceptive processing, which was greater in the SBI group than in the no SBI group. This finding most likely explains the subjective symptoms of imbalance in patients with MS with normal CBT.

Cataract and cognitive impairment: a review of the literature

Acquired cataract and cognitive impairment are both common age-related problems, and ophthalmologists are increasingly likely to encounter patients who have both. Patients with dementia types who display early visuoperceptual impairment may present first to ophthalmology services. When these patients have coexisting cataract, it may be difficult to distinguish visual complaints due to cataract from those due to dementia. The interaction between visual impairment due to cataract and neurodegenerative disorders affecting the central visual pathways, is not fully understood. Visual impairment due to cataract may stress impaired attentional mechanisms and cataract extraction may improve cognitive performance in some patients with early cognitive impairment; however, the benefits of cataract surgery in established dementia are less clear. In this study, the literature on this subject was reviewed and the implications for practice were considered.