Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns.

BACKGROUND: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits. OBJECTIVE: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns. METHODS: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions). RESULTS: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function. CONCLUSION: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.

Left hemispheric neuronal heterotopia: a PET, MRI, EEG, and neuropsychological investigation of a university student.

A 21-year-old left-handed medical student had a prominent unilateral cerebral cortical malformation due to an ontogenetic migration disorder. We performed neuropsychological studies, EEG, T1- and T2-weighted and proton-density MRI, and positron emission tomography (PET) (under both the resting condition and neuropsychological activation). Neuropsychological testing revealed normal intelligence and generally normal memory functioning but selective deficits in tests of verbal fluency and spatial-figural relationships. Proton-density and T2-weighted MRI revealed extensive left cortical heterotopia that included parts of the Wernicke area. PET under the resting condition revealed a small interhemispheric difference with slightly reduced glucose metabolism in the left temporoparietal cortical zone. An activation PET (with the patient performing a verbal fluency test) resulted in a normal overall increase in metabolism but marked deviations in cortical areas. The highest activity changes were in the Broca and Wernicke areas of the right hemisphere, and there was very little activation in those regions of the left hemisphere that were expected to respond well to the activation--the temporal, parietal, and temporo-occipital cortical zones. We conclude that there can be large compensations for unilateral heterotopia.

Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics. Initial results from a new brain collection.

Volumes of the hippocampal formation, external and internal pallidum, caudate, putamen, and nucleus accumbens were measured in both hemispheres of recently collected post-mortem brains of 18 chronically ill schizophrenics and 21 control subjects. In the schizophrenic group, the hippocampal formation and the internal pallidum were significantly smaller in the right and left hemisphere, whereas external pallidum, putamen, caudate and accumbens were not significantly changed. Volumes of the hippocampus and of all evaluated parts of the basal ganglia were in the male schizophrenics more reduced than in the female patients. The right and left hemispheres were equally affected in both sexes. Since the mean brain weight was in patients and controls nearly identical, the volume differences can not be explained by a general brain atrophy or hypoplasia but rather indicate a more focal lack of brain tissue, by which some clinical features of the disease might be explained.

[Acute postoperative psychosyndromes. A prospective study and multivariate analysis of risk factors]. / Akute postoperative Psychosyndrome. Eine prospektive Studie und multivariate Analyse von Risikofaktoren.

The incidence of postoperative delirium was assessed in 92 patients on a general surgical intensive care unit. Postoperative delirium was diagnosed in 39 patients (42%). Most of the cases were diagnosed on the second postoperative day and the median duration was seven days. Ten patients with delirium (25%) had a lethal outcome, compared to a 13% mortality of the whole population. In univariate analysis the variables age, preoperative therapy for heart failure, respirator therapy, dobutamin therapy and lowest capillary pO2 on day one were significantly associated with later development of delirium, whereas preoperative peritonitis, and history of stroke or hypertension were only borderline significant. A predictive model with three parameters emerged from multiple logistic regression analysis: after correction for age (p = 0.001), respirator therapy (p = 0.020), and capillary pO2 on day one (p = 0.049) none of the remaining variables proved of additional significance. The statistical model yielded a predictive accuracy of 78%.

[The structure of mnestic problems in multiple sclerosis: everyday memory performance and neuroradiologic findings]. / Zur Struktur mnestischer Probleme bei Multipler Sklerose--Alltagsgedächtnisleistungen und neuroradiologische Befunde.

35 multiple sclerosis patients and 30 matched healthy controls were investigated for mnestic problems using a German everyday memory test. The objects were both the description of structural characteristics of disturbances and "ecological validity" to meet rehabilitative issues prospectively. In the MS group, impairments were found mainly in the memory domain under delayed recall conditions of complex material. The processing of these tasks may be especially sensitive against fiber tract lesions. While discrete lesions, mostly found in patients with relapsing-remitting courses, inconsistently lead to partial memory disturbances, global mnestic deficits are to be expected in confluent lesion patterns exceeding a critical "threshold of cerebral tolerance." The latter characterises mostly patients with chronic progressive disease courses.

[Therapy of pain syndromes in multiple sclerosis -- an overview with evidence-based recommendations]. / Therapie von Schmerzen bei MS -- eine Ubersicht mit evidenzbasierten Therapieempfehlungen.

While pain is a common problem in multiple sclerosis (MS) patients, it is frequently overlooked and has to be asked for actively. Pain can be classified into 4 diagnostically and therapeutically relevant categories. 1. PAIN DIRECTLY RELATED TO MS: Painful paroxysmal symptoms like trigeminal neuralgia or painful tonic spasms are treated with carbamazepine as first choice, or lamotrigine, gabapentin, oxcarbazepine and other anticonvulsants. Painful "burning" dysaesthesia, the most frequent chronic pain syndrome, are treated with tricyclic antidepressants or carbamazepine, further options include gabapentin or lamotrigine. While escalation therapy may require opioids, the role of cannabinoids in the treatment of pain still has to be determined. 2. PAIN INDIRECTLY RELATED TO MS: Pain related to spasticity often improves with adequate physiotherapy. Drug treatment includes antispastic agents like baclofen or tizanidine, alternatively gabapentin. In severe cases botulinum toxin injections or intrathecal baclofen merit consideration. Physiotherapy and physical therapy may ameliorate malposition-induced joint and muscle pain. Moreover, painful pressure lesions should be avoided using optimally adjusted aids. 3. Treatment-related pain can occur with subcutaneous injections of beta interferons or glatiramer acetate and may be reduced by optimizing the injection technique and by local cooling. Systemic side effects of interferons like myalgias can be reduced by paracetamol or ibuprofen. 4. Pain unrelated to MS such as back pain or headache are frequent in MS patients and may be worsened by the disease. Treatment should be follow established guidelines. In summary, a careful analysis of the pain syndrome will allow the design of the appropriate treatment plan using various medical and non-medical options and thus will help to ameliorate the patients' quality of life.

Cranial magnetic resonance imaging in multiple sclerosis--indicated only in exceptional cases?

Clinical examination, spinal fluid laboratory data, evoked potentials (EP), cranial computed tomography (CT), and magnetic resonance imaging (MRI) were compared for their value in diagnosing multiple sclerosis (MS) in 51 patients aged 18-60 yrs. MRI was superior to CT imaging: supratentorial lesions were found in 90% of the patients with confirmed MS. These lesions are not specific, however, as vascular processes, vitamin B12 deficiency or chronic encephalitis, can show similar MRI-patterns. The detection of infratentorial lesions in symptomatic patients was poor (8% compared to 64% pathological EP-findings). Thirty-eight patients (= 75%) could be classified correctly as "confirmed MS" according to Bauer-criteria without any CT or MR imaging. In the remaining 13 patients presenting classificatory problems due to normal CSF, first manifestation or possible alternate processes, MRI helped for the final diagnosis in only 6 cases. The value of MRI in diagnosing MS seems to lie in its superiority to CT in excluding other pathological processes or for research rather than in its value for the confirmation of the diagnosis. In a minority of cases, it can detect supratentorial lesions in patients with pure spinal symptoms, normal CSF, or first manifestations.

Further aspects of MR-signal enhancements in stenosis of the cervical spinal canal. MRI-investigations in correlation to clinical and cerebrospinal fluid (CSF) findings.

The validity and anatomical basis of increased MR-signal intensity of the cord in cervical canal stenosis is discussed with respect to our own data of 32 patients (including results of clinical, CSF and other imaging technique findings) and previous reports. A shear-stress hypothesis with edematous tissue changes is favoured.

The myelon in cervical spinal canal stenosis: imaging by X-ray and MRI.

Methods which produce findings relevant to diagnosis and therapy of cervical vertebral canal stenosis are described. Especially MRI provides insights into the structure of the myelon; abnormal image signals may possibly correlate with cervical myelopathy based on disorders of microcirculation.

Magnetic resonance imaging (MRI), cranial computerized tomography (CCT), evoked potentials and cerebrospinal fluid (CSF) analysis in five patients with funicular myelosis.

Five Patients with vitamin B12 deficiency were examined by means of MRI, CCT, VEP, BAEP, EEG, and CSF. In 3 patients medianus-SEP and EMG/ENG were recorded as well. Partly, findings of MRI, CCT, VEP, BAEP, SEP, and CSF were similar to those in multiple sclerosis. This is not very surprising considering that the central nervous system lesions in vitamin B12 deficiency consist of disseminated demyelination. Because of this all these investigative techniques must be considered non-specific. Appraisal of findings is only possible in connection with the case history, clinical findings, and supplementary diagnostic measurements.

[Metachromatic leukodystrophy. Results of laboratory chemical, neurophysiologic, histologic and imaging procedures within the scope of a family study]. / Metachromatische Leukodystrophie. Ergebnisse laborchemischer, neurophysiologischer, histologischer und bildgebender Verfahren im Rahmen einer Familienuntersuchung.

Examining the members of a family the validity of chemical analysis, neurophysiology and neuroimaging for the diagnosis of metachromatic leukodystrophy (MLD) is discussed. As the arylsulfatase A is not decreased in all cases, the neuroimaging (cranial computerized tomography--at a less extend magnetic resonance imaging) gains a particular diagnostic significance. But neither for neuroimaging nor for neurophysiological findings the results are specific. The histological findings have to back up the diagnosis.

Relationship of nuclear magnetic resonance examinations to clinical data, cerebrospinal fluid findings and visual evoked potentials in multiple sclerosis.

We examined 150 patients with a 0.5 Tesla MR system. Fourteen patients were excluded from the study, because, in addition to the clinical signs of multiple sclerosis, they showed other abnormalities (spinal canal narrowing, embolic disease, Vitamin B12 deficiency, etc.). The results of the 136 examinations were related to the duration of disease, index of impairment on Kurtkze's disability scale, the clinical course, and the CSF and VEP results. The MR studies were evaluated in a semiquantitative manner. Patients with a long duration of disease demonstrated more changes than did cases with a short course. We found more periventricular confluences and more white matter plaques in the centrum semiovale. In addition, more lesions were seen in patients with a severe course of disease. All patients with negative CSF results (n = 13) showed positive MR examinations, and vice versa, patients with positive CSF findings showed negative MR results (n = 5). First results of a follow-up study demonstrate that most abnormalities in MR are not related to the clinical course or therapeutical procedure.

[Differential diagnosis of juvenile stroke. A case of moyamoya]. / Zur Differentialdiagnose des "juvenilen Schlaganfalls". Ein Fall von Moyamoya.

Stroke before the age of 40 years is unusual and its etiology often different from that in older people. In a 29-year-old man the cause of a stroke was revealed to be bilateral vascular malformations at the base of the brain, an example of the moyamoya syndrome, rare among Europeans and published in German-speaking countries only in a few single case reports.

The cognitive-mnestic performance profile of a patient with bilateral asymmetrical thalamic infarction.

The case of a 46-year old patient with a bilateral medial thalamic infarct, affecting mainly the region of the internal medullary lamina, but not of the mammillothalamic tract, is documented neuropsychologically and neuroradiologically. Testing was done after acute remission. The patient was of average intelligence but manifested a number of verbal memory problems. These are most likely attributable to the selective diencephalic damage and are interpreted as a disconnection syndrome.

[Quantification of postoperative vigilance by evoked potentials]. / Quantifizierung der postoperativen Vigilanz mittels evozierter Potentiale.

OBJECTIVE: Patients will be discharged from the postoperative recovery room mostly on subjective clinical assessment. In this study an approach to a more quantitative judgment of postoperative vigilance is made by recording the P300-latency and neuropsychological tests. METHODS: 22 adult patients undergoing a disc operation were examined. For induction of anesthesia thiopental (4-5 mg/kg), fentanyl (0.1 mg) and a musclerelaxant (atracurium 0.4 mg/kg or succinylcholine 1-2 mg/kg after precurarisation with atracurium 5 mg) were given. Anesthesia was then continued with enflurance (1.0-1.2 MAC) in a mixture of 67% nitrous oxide in oxygen. If postoperative analgesia was needed, piritramid was injected in boli à 3-6 mg. The P300 was acoustically stimulated with an oddball-paradigm and recorded at Fz and Cz. Afterwards the latencies were measured and compared with a vigilance score composed of clinical parameters and neuropsychological tests. Recordings were done preoperatively and every 30 minutes up to 2 hours postoperatively. A correlation between P300-latencies and vigilance score was made with the coefficient of Spearman. Comparison of pre- and postoperative values was managed by using Wilcoxon test for matched pairs with Bonferroni-correction. RESULTS: Immediately after operation, P300 was obtained only in 8 patients (36%). The latencies were delayed (394 +/- 35 ms versus 326 +/- 12 ms preoperatively). During follow-up patients recovered and 2 hours postoperatively only one patient had no P300. At the end of the examination period P300-latencies of most patients had not yet reached the preoperative levels. The vigilance score in parallel showed decreases immediately after the operation and increases later on. However there were discrepancies between P300 latencies and neuropsychological findings, in some cases possibly due to the sedative effects of postoperative analgetics. CONCLUSION: Recording of P300-latencies showed remarkable cognitive deficits because of subclinical anesthesia hangover even 2 hours after a routine inhalational anesthesia. It is a good quantifiable method for assessment of postoperative vigilance. In some cases P300-latency is a more sensitive parameter for vigilance phenomena than clinical and neuropsychological scores.

Searching for the anatomical basis of retrograde amnesia.

The case of a patient with profound retrograde and minor anterograde amnesia is described and used to discuss the kind of brain damage which will most likely result in persistent retrograde amnesia as the principal symptom. The patient was an industrial manager who had fallen off a horse four years prior to the present neuropsychological and neuroradiological investigation. MRI examination revealed an injury to both temporal poles and to the latero-ventral portion of the right prefrontal cortex. The prefrontal and temporal cortical damage on the right side deeply invaded the white matter while the temporal cortical damage on the left side was much smaller; here, however, portions of the temporo-parietal transition zone were affected as well. The patient was of average intelligence. His attention, short-term memory, and learning ability were average or somewhat below average. His old memories were severely affected in the personal-episodic domain, and much less so in that of semantic remote memory. We conclude from this case that the necessary anatomical substrate for the retrieval of old episodic memories lies within the anterior temporal regions (including deeper situated fiber projections) and possibly involves an interaction with the prefrontal cortex, and that this damage is dissociable from the medial temporal-lobe damage leading to anterograde amnesia.

Retrograde amnesia after traumatic injury of the fronto-temporal cortex.

An industrial manager had severe retrograde and variable but usually mild anterograde amnesia four years after a head injury. MRI showed damage of both temporal poles and the lateral portion of the right prefrontal cortex. The prefrontal and temporal cortical damage on the right side extended deeply into the white matter while the temporal cortical damage on the left side was much smaller. There was an additional left temporo-parietal lesion. The patient was of average intelligence. His attention, short term memory and learning ability were average or somewhat below average. His old memories were severely affected for the personal-episodic domain and less so for semantic remote memory abilities. Therefore an anatomical dissociation between anterograde and retrograde amnesia is possible at the anterior temporal regions, possibly interacting with the prefrontal cortex; these regions seem necessary for the retrieval of old episodic memories.