[Short and simple is not always better: limitations of cognitive screening tests]. / Kurz und einfach ist nicht immer besser: Grenzen kognitiver Demenzscreenings.

The increasing prevalence of Alzheimer's dementia (AD) and limited resources in outpatient care have encouraged the distribution of cognitive screening tests, in spite of their frequently unsatisfying accuracy regarding the differentiation between incipient AD, depression and age-associated memory impairment. 8 patients with probable AD and 17 controls completed a neuropsychological follow-up two years after initial examination. Beside four screening tests a memory based testing-the-limits (TtL) paradigm as well as the German version of the California Verbal Learning Test were administered. Based on hierarchical cluster analysis we could demonstrate that only well elaborated tests, such as a plasticity based TtL paradigm, did classify AD-patients correctly. The findings confirm reservations against cognitive screening procedures in detecting dementia and suggest that dynamic test strategies offer a powerful diagnostic alternative to traditional status-oriented tests.

[Inclusion body myositis, Paget's disease of the bone and frontotemporal dementia: early involvement of the heart and respiratory muscles]. / Inclusion Body Myositis mit Morbus Paget und frontotemporaler Demenz: frühe Beteiligung des Herzens und der Atemmuskulatur.

Since valosin-containing protein mutations were reported as a cause of hereditary inclusion body myositis associated with Paget's disease of the bone and frontotemporal dementia, many new mutations have been described in the last decade. We report on a 46-year-old German male with a progressive tetraparesis and autosomal dominant inheritance pattern. Echocardiography revealed a beginning dilated cardiomyopathy and laboratory analyses showed increased alkaline phosphatase. Decreased verbal memory and an impairment of concept building were observed on neuropsychological examination. Muscle biopsy demonstrated a myopathic pattern, rimmed vacuoles, CD8+ T-cell infiltrates and positive MHC1-muscle fibres. We found a heterozygote mutation in exon 5 of the valosin-containing protein gene (c.464G > T p.Arg155Leu), which until now has been described only in an Australian family. We describe here the first German case with the above-mentioned mutation causing inclusion-body myositis associated with Paget's disease of the bone and fronto-temporal dementia. Here, we recommend regular controls of cardiac and respiratory functions.

Hippocampal cavities are not associated with cognitive impairment in transient global amnesia.

BACKGROUND: Hippocampal sulcal cavities (HSC) have been speculated to contribute to a higher vulnerability of memory pathways and might be a possible etiological factor in transient global amnesia (TGA). Therefore, we evaluated the influence of HSC on cognitive long-term outcome in TGA-patients. METHODS: Fourteen otherwise healthy patients with the clinical syndrome of TGA in their history underwent a high-resolution magnetic resolution imaging and a comprehensive neuropsychological test battery. The neuropsychological control group consisted of 15 healthy subjects and was balanced for age, sex and other risk factors as well as intellectual and social status. RESULTS: Magnetic resolution imaging and neuropsychological testing have been performed 1128 days (median) after the TGA. HSC have been detected in nine of the 14 patients and have been bilateral in eight of them. There were no differences in cognitive performance in patients with and without HSC as well as compared to healthy subjects. Even in patients with greater lesion load, only a slight visuospatial deficit was found. CONCLUSIONS: Although an increased incidence of HSCs is detected in TGA patients, cavities are not obligatorily in TGA. Moreover, even patients with hippocampal cavities achieve a full neuropsychological recovery independent of the frequency and size of the hippocampal lesions.

A novel presenilin1 mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF.

BACKGROUND AND PURPOSE: A novel presenilin1 (PSEN1) mutation associated with dementia and spastic paraplegia in a family with five affected individuals is described. The index patient was a 35-year-old man presenting with cognitive decline, behavioural symptoms, dysarthria, and gait disorder due to spasticity. METHODS AND RESULTS: Genetic analysis revealed a missense mutation Gln223Arg in exon 7. Initial CSF analysis revealed drastically decreased Abeta42 level despite marginally decreased FDG metabolism. CONCLUSION: Cerebrospinal fluid biomarker analysis might point towards genetic analysis of PSEN1 in patients with positive family history and age of onset below 60 years.

[Depressive symptoms in a case of "posterior cortical atrophy"]. / Depressive Symptome als Erstmanifestation einer posterioren kortikalen Atrophie.

Posterior cortical atrophy (PCA) is a neurodegenerative disease which leads to a dementing syndrome that involves an irreversible impairment of higher visual and spatial functions. Memory and language functions generally tend to be preserved better than in other types of dementia including Alzheimer's disease. Here we report a case of PCA, which initially was diagnosed and treated for about a year as a major depressive episode. While most patients initially present with neurologic symptoms, in some PCA cases secondary manifestations, such as e. g. affective symptoms, might appear before the onset of overt cognitive dysfunction. In some cases, this might lead to a diagnostic delay of this neurodegenerative disease.

The Wada test in Austrian, Dutch, German, and Swiss epilepsy centers from 2000 to 2005: a review of 1421 procedures.

Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.

Transient global amnesia--full recovery without persistent cognitive impairment.

Transient global amnesia (TGA) is a clinical syndrome of unknown etiology characterized by sudden onset anterograde amnesia, which was thought to resolve completely. However, some authors have also suggested permanent memory impairment. It is unclear whether these results reflect a true persistent damage or a simply too short assessment interval in the context of a prolonged recovery phase after TGA. To evaluate the cognitive long-term outcome, 16 patients who had suffered from TGA at a mean of 3 years before and 15 healthy controls underwent a comprehensive neuropsychological test battery. No significant differences between patients' and controls' cognitive performance were found, irrespectively of the analyzed neuropsychological domain. Therefore we hypothesize that TGA usually does not cause persistent cognitive deficits due to a generally transient and prognostic benign character.

Lyme neuroborreliosis disguised as normal pressure hydrocephalus.

A 74-year-old woman presented with gait impairment, urinary incontinence, and dementia. She showed lymphocytic CSF pleocytosis and pronounced intrathecal Borrelia burgdorferi antibody production, indicating active Lyme neuroborreliosis. The syndrome of normal-pressure hydrocephalus (NPH) fully remitted after ceftriaxone treatment. Lyme neuroborreliosis may cause NPH by interfering with subarachnoid CSF flow.

Cerebral involvement in McLeod syndrome.

McLeod syndrome is an Xp21-linked Kell blood group variant due to lack of erythrocyte protein Kx with associated RBC membrane dysfunction such as acanthocytosis. A man with this syndrome developed chorea and slight neuropsychological impairment. He had caudate atrophy on cerebral imaging and reduced striatal dopamine D2-receptor binding on single-photon emission computed tomography. Since Xp21 was partly deleted in the patient, the missing gene product (possibly Kx) may be essential for the integrity of the striatum.

Quantitative MRI in CADASIL: correlation with disability and cognitive performance.

OBJECTIVE: To study correlations between total lesion load on brain MRI and clinical features, and to evaluate the influence of demographic variables on quantitative MRI variables in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: CADASIL is a hereditary form of small-vessel disease caused by mutations within the Notch3 gene. MRI abnormalities have been found both in asymptomatic and symptomatic CADASIL individuals. METHODS: Quantitative measurements on cerebral MRI were performed in 64 CADASIL individuals. MRI lesions were quantified using a semi-automated segmentation technique based on local thresholds. RESULTS: MRI total lesion volume correlated significantly with disability (Rankin Scale) on both T1- and proton density (PD)-weighted images. There was a significant inverse correlation between total lesion volume and overall cognitive performance as determined by the Mini-Mental State Examination. Age but not sex was correlated with lesion load both on T1- and PD-weighted images. There was no detectable influence of the Notch3 genotype on quantitative MRI variables. CONCLUSIONS: This study demonstrates correlations between MRI lesion volume and clinical characteristics in CADASIL. Longitudinal studies are now warranted to investigate whether quantitative MRI could be used as an adjunct outcome measure in future therapeutic trials in CADASIL.

Muscle and skin biopsies are a sensitive diagnostic tool in the diagnosis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a microangiopathic syndrome. Although the defective gene has been identified, genetic analysis may be effort some due to its large size and various mutations. Providing a reliable diagnostic marker would therefore be helpful. Electron microscopy has revealed characteristic electron-dense granular deposits in the basal lamina of vessels of patients with CADASIL. We investigated the sensitivity of skin and muscle biopsies for diagnosing CADASIL. We examined 30 family members of three unrelated German families affected by CADASIL. In 14 of the 21 affected individuals we performed skin and muscle biopsies; two patients were clinically asymptomatic. Under electron microscopy all muscle and skin biopsy specimens showed patches of granular and electron-dense material in the basal layer of both arterioles and capillaries. These findings confirm that general microangiopathy is a typical feature of this syndrome and is present in the early phase of the disease with or without clinical manifestation. Thus, as electron microscopy of skin biopsy specimens can establish the diagnosis of CADASIL with high certainty, it may be considered the method of first choice.

Characteristic MR lesion pattern and correlation of T1 and T2 lesion volume with neurologic and neuropsychological findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an arteriopathy related to a genetic defect of the notch 3 gene on chromosome 19. The purpose of this study was to evaluate lesion distribution and volume using MR imaging and to correlate the lesion volume with the neurologic and neuropsychological findings. METHODS: Twenty members of two families (14 with CADASIL as determined by linkage analysis, six healthy) were studied with MR imaging. Two observers evaluated the MR findings semiquantitatively and quantitatively. MR results were then correlated with neurologic and neuropsychological findings. RESULTS: A typical pattern of lesion distribution in patients with CADASIL was found: the frontal lobe was the site with the highest lesion load, followed by the temporal lobe and the insula. The total lesion volume on T1-weighted MR images correlated significantly with the degree of disability and the degree of impairment in neuropsychological functions (including attention, memory, and conceptual and visuospatial functions). CONCLUSION: In CADASIL patients, a common pattern of cerebral lesion distribution is found. The total T1 lesion volume is an important parameter to correlate with disability, as it may prove to be helpful in predicting the natural history of the disease.

[Effects of high-dose cortisone therapy on cognition]. / Hochdosiskortisontherapie und Kognition.

Treatment with high-dose corticosteroids over 3-5 days reduces the duration and severity of relapses in patients with multiple sclerosis. Since the benefit of this treatment appears to be dose-dependent, application of ultrahigh steroid doses becomes important. On the other hand, data from basic research and clinical studies indicate potential side effects on mnestic functions. Three recently published studies show that treatment with pulsed corticosteroids induces reversible impaired memory. The effects were independent of the dose administered.

Quantitative evaluation of mirror movements in adults with focal brain lesions.

Mirror movements (MM), involuntary movements of homologous muscles opposite to unilateral limb activity, decrease in the course of motor development, but may reappear in adults after brain damage. To better characterize this type of acquired MM, grip forces of 36 healthy subjects and 35 patients suffering from focal brain lesions were compared. Holding force transducers in a pinch grip between thumb and index fingers of each hand, subjects had to repeatedly change the grip force in one hand, whilst the other (mirror) hand just had to prevent the manipulandum from dropping. In a second task, force changes had to be produced either in a symmetric or in an antiparallel manner. No significant group differences between patients and controls in the extent of coupling were found. During unimanual squeezing, only six patients had a co-activation in the pathologic range. Whilst performing bimanual asymmetric grip force changes, pathologic coupling was seen only in five patients. No association was found between the presence of pathologic MM and clinical or neuroanatomical features. Brain lesions in adults seem only rarely to be associated with pathologic MM. They might be non-specific and not related to the characteristics of the lesion.

Reversible impaired memory induced by pulsed methylprednisolone in patients with MS.

Thirty patients with multiple sclerosis were randomized to 500 or 2,000 mg of methylprednisolone (MP) over 5 days. They were prospectively studied neuropsychologically before and at days 6 and 60 after onset of the therapy, using a double-blind study design. Patients showed selective deterioration of declarative memory retrieval at day 6, which was fully reversible at day 60. Although the sample size was small, these effects were independent of the administered MP dose.

[Cognitive impairment in adults with neurofibromatosis type 1]. / Kognitive Einschränkungen bei erwachsenen Patienten mit Neurofibromatose Typ 1.

Cognitive impairment is a common phenomenon in children with neurofibromatosis type 1 (NF1), but only little is known about its nature and frequency in adult NF1-patients. Using a comprehensive psychometric test battery, we investigated 20 patients with NF1 and 20 age and gender matched control subjects without neurological diseases. Results showed slightly lowered test scores in patients compared with controls but no specific intellectual impairment. On a computerized test of selective attention, the NF1-group had significant slower reaction times. Also, three out of four memory tests and a test of visuoconstructive abilities showed poorer test results in the NF1-patients. Executive functions however were not affected. The findings agreed well with the test profile in NF1-children and supported the idea of a continuum between childhood and adulthood. Observations are discussed in the context of studies investigating the association of cognitive deficits with either intracranial lesions or alterations in the neurofibromin expression.

[Type I neurofibromatosis. A model for the study of molecular principles of cognition]. / Neurofibromatose Typ I. Ein Modell für die Untersuchung molekularer Grundlagen von Kognition.

Cognitive impairment in neurofibromatosis type I (NF1) has only recently attracted interest. In addition to previous studies in children, our own investigation of 20 patients confirms the slightly lowered psychometric test scores also for adults with NF1. Molecular manipulation of the neurofibromin gene leads to learning disorders in the mouse model ("cognitive neurogenetics"). It is not just faulty brain development that underlies these findings: neurofibromin plays a role in signal transduction cascades that are active during learning and memory throughout the life span. Thus, it appears possible to cure the cognitive defects at least in the mouse ("cognitive enhancement"). In man, an early diagnosis of NF1 is presently essential in order to provide specific remedial education for children affected by the learning disorder of neurofibromatosis type I.

[Hereditary CADASIL cerebral arteriopathy. Report of a family]. / Erbliche zerebrale Arteriopathie CADASIL. Beschreibung einer Familie.

We describe two members of a German family with cerebral autosomal dominant arteriopathy (CADASIL), which is characterized by recurrent subcortical ischemic strokes, mild dementia and leukoencephalopathy. The clinical features of the disease are suggestive of Binswanger's subcortical arteriosclerotic encephalopathy. However, it differs by the lack of hypertension and familial aggregation with autosomal dominant inheritance. Magnetic resonance imaging (MRI) of the brain shows subcortical ischemic infarcts affecting the periventricular white matter, the basal ganglia and the brain stem. On T2-weighted imaging, areas of hyperintensity were found in the white matter of both cerebral hemispheres with preponderance of frontal and anterotemporal regions. We assume that the underlying disease in this family is CADASIL with subcortical infarcts and leukoencephalopathy. The recently assigned disease locus on chromosome 19 was confirmed in this family. A treatment trial with acetylsalicylate was started in the affected members of the family.

Hypersomnia associated with bilateral posterior hypothalamic lesion. A polysomnographic case study.

We examined an obese 58-year-old patient with a bilateral posterior hypothalamic lesion of unknown etiology. A 24-hour polysomnography revealed a markedly increased total sleep time (17.6 h). During daytime, only 3 continuous wake phases occurred. REM periods occurred only between 5 p.m. and 6 a.m. We conclude from our results that, similar to the results from animal experiments, the posterior hypothalamus in humans plays a critical role in the maintenance of wakefulness.