Claudius Bartels

Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis

In skeletal muscle homogenates of 14 patients with sporadic amyotrophic lateral sclerosis, an approximately twofold lower specific activity of NADH:CoQ oxidoreductase in comparison to an age matched control group (n=28) was detected. This finding was confirmed by a detailed analysis of mitochondrial oxidative phosphorylation in skeletal muscle using saponin-permeabilized muscle fibers. (i) A significantly lowered maximal glutamate+malate and pyruvate+malate supported respiration of saponin-permeabilized fibers was detected in the patients group. (ii) Titrations with the specific inhibitor of NADH:CoQ oxidoreductase amytal revealed a higher sensitivity of respiration to this inhibitor indicating an elevated flux control coefficient of this enzyme. (iii) Applying functional imaging of mitochondria using ratios of NAD(P)H and flavoprotein autofluorescence images of saponin-permeabilized fibers we detected the presence of partially respiratory chain inhibited mitochondria on the single fiber level. A secondary defect of mitochondrial function due to the neurogenic changes in muscle seems to be unlikely since no mitochondrial abnormalities were detectable in biopsies of patients with spinal muscular atrophy. These results support the viewpoint that an impairment of mitochondria may be of pathophysiological significance in the etiology of amyotrophic lateral sclerosis.

Neuropsychological sequelae of diffuse traumatic brain injury

Primary objectives: Description and analysis of neuropsychological deficits following brain trauma with diffuse lesion probably corresponding to diffuse axonal injury (DAI).Research design: A series of 111 patients suffering from traumatic brain injury could be investigated neuropsychologically within the first 4 weeks after injury and re-assessed after 5–8 months. They included 11 subjects with CT-evidence of diffuse axonal injury, but no CT-signs of focal contusions. Eleven patients with focal frontal contusions but no CT signs of DAI were matched to and compared with the DAI subjects. Seventeen TBI patients with normal CT scans served as controls.Results: When assessed within the first 4 weeks after TBI, both DAI and frontal contusion patients exhibited behavioural abnormalities and deficits in Wechsler Similarities. The DAI patients were also impaired in Digit Span backward and Stroop interference. When re-assessed, the DAI patients showed considerable deficits in the California Verbal Learning Test and in the Wisconsin Card Sorting Test.Conclusions: DAI leads to neuropsychological impairment dominated by executive and memory dysfunction.

Poststroke Depression Is There a Pathoanatomic Correlate for Depression in the Postacute Stage of Stroke

BACKGROUND AND PURPOSE This study is aimed at the pathoanatomic correlates of depression in the postacute stage of patients with stroke. METHODS Of a consecutive series of 104 stroke patients, a subgroup of 47 patients with single demarcated unilateral lesions was selected. Clinical examination, neuroradiological CT scan examination, and psychiatric assessment were performed within a 2-month period after the acute stroke. Depression was assessed with the Cornell Depression Scale, the Montgomery-Asberg Depression Rating Scale, and according to modified DSM-III-R criteria. The neuroradiological examination of all patients was performed on the same scanner, and lesion location, lesion volume, and ventricle-to-brain ratio were analyzed. RESULTS We found no significant differences in depression scores between patients with left and right hemisphere lesions and no correlation between the severity of depression and the anteriority and the volume of lesion or brain atrophy. Major depressive disorders were only found in nine patients with left hemisphere lesions, all involving the basal ganglia, whereas none of the patients with right hemisphere stroke exhibited major depression. CONCLUSIONS Lesions in the vicinity of the left hemisphere basal ganglia tend to play a crucial role in the development of major depression after the acute stage of stroke. The pathophysiological implications of this finding are discussed.

Depression in acute and chronic aphasia: symptoms, pathoanatomical-clinical correlations and functional implications.

Depressive alterations were investigated in 21 acute and 21 chronic aphasic patients with single left sided strokes. The assessment of depression was based on a psychometrically evaluated German version of the Cornell Scale for Depression (CDS) and the Research Diagnostic Criteria (RDC). No significant difference was found concerning depression sum-scores between the two aphasic groups. The acute group, however, exhibited significantly higher ratings in items related to physical signs of depression and disturbances of cyclic functions. Patients corresponding to the RDC-syndrome of major depression were only found in the acute group. Neither age, sex nor degree of hemiparesis discriminated the patients on the severity of depressive symptoms. In the acute patient group, nonfluency of aphasia was the only parameter that could be identified which had an effect on the mood symptom scores. A CT scan analysis in the acute patient group showed an association between the severity of depression and anterior lesions. A significant correlation was found between CDS sum-scores and the proximity of the anterior border of the lesion to the frontal pole of the hemisphere whereas the volume of lesions seemed to have no effect on depressive alterations in acute aphasic patients. Superimposition of the lesions of the aphasic patients with major depressive disorders showed a common subcortical lesion area involving putaminal and external pallidal structures.

The impact of aphasia on the patient and family in the first year poststroke

This article reports a study that addressed coping strategies and possible related factors in 58 patients with aphasia and their relatives in the first year poststroke. Coping strategies, psychosocial changes, expectations of psychosocial adjustment, illness-related causal attributions, control beliefs, and activities of daily living were investigated in a longitudinal study. The data show that subjects with aphasia and their relatives experience significantly more severe professional and social changes than do subjects without aphasia and their families. Aphasia, however, seems to have no substantial effect on coping strategies, expectancies of adjustment, causal and control attributions, or activities of daily living as measured by the Barthel Index.

Complement-associated neuronal loss in a patient with CASPR2 antibody-associated encephalitis.

Recently, CASPR2 antibody–associated encephalitis was presented as a subentity of encephalitis with antibodies against the voltage-gated potassium channel (VGKC) complex. Besides limbic encephalitis, CASPR2 antibodies are also found in Isaac syndrome and Morvan syndrome.1,2 The specific underlying pathogenic mechanisms in limbic encephalitis are unknown. Our data suggest an antibody- and complement-mediated pathology in CASPR2 antibody–associated encephalitis.

Unusual presentations of patients with the mitochondrial MERRF mutation A8344G

MERRF is typically characterized by myoclonus, generalized seizures and ragged-red fibers in muscular biopsy. We report a family (harbouring the A8344G mutation) with a late onset of the disease and an uncommon clinical manifestation, including episodes of reversible respiratory failure, the presence of ophthalmoplegia, and the absence of seizures and myoclonus in most subjects. We conducted histochemical, biochemical and molecular genetic studies. Mutation analysis revealed that the level of mutated mitochondrial DNA (mtDNA) was above 80% in the skeletal muscle of all siblings. Nevertheless, one severely affected individual did neither present cytochrome c oxidase-negative fibers nor ragged-red fibers in the skeletal muscle biopsy. These data extend the phenotypic range associated with the MERRF syndrome. We suggest that the analysis of mtDNA could be of importance in many cases of unclear multisystem disorders in later life.

Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

BackgroundRadiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide.Case PresentationThe case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed.ConclusionsIn this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy.

Inherited cerebellar diseases.

This chapter analyzes the neuropsychological deficits in inherited cerebellar diseases and compares their symptomatology with animal models in which the exact anatomical localization of degeneration is known and limited to the cerebellum. Both animal and human data suggest that cerebellar cortical atrophy affects functions of the frontal lobe system. Olivopontocerebellar atrophy is genetically and clinically in homogeneous. The dementia syndrome that occurs in a proportion of patients does not seem to be linked with cerebellar dysfunction. Patients suffering from Friedreichs disease have been described as exhibiting cognitive slowing and deficits in spatial tasks. Because other structures are more prominently involved than the cerebellum in this disease, other pathoanatomical correlates may explain the symptomatology.

Freud's impact on aphasiology--aphasiology's impact on Freud.

In 1891, Sigmund Freud published a book on aphasia. Although Freuds contribution to aphasiology could have been important in retrospect, it was hardly acknowledged for three quarters of a century. It may have had an impact on psychoanalytic theory, but this was not acknowledged by Freud. If there are neurological roots in psychoanalysis, they are buried by paradigmatic shifts in Freuds theory.