Anne-Marie Landtblom

Sudden onset headache: a prospective study of features, incidence and causes

Sudden onset headache is a common condition that sometimes indicates a life- threatening subarachnoid haemorrhage (SAH) but is mostly harmless. We have performed a prospective study of 137 consecutive patients with this kind of headache (thunderclap headache = TCH). The examination included a CT scan, CSF examination and follow-up of patients with no SAH during the period between 2 days and 12 months after the headache attack. The incidence was 43 per 100 000 inhabitants > 18 years of age per year; 11.3% of the patients with TCH had SAH. Findings in other patients indicated cerebral infarction (five), intracerebral haematoma (three), aseptic meningitis (four), cerebral oedema (one) and sinus thrombosis (one). Thus no specific finding indicating the underlying cause of the TCH attack was found in the majority of the patients. A slightly increased prevalence of migraine was found in the non-SAH patients (28%). The attacks occurred in 11 cases (8%) during sexual activity and two of these had an SAH. Nausea, neck stiffness, occipital location and impaired consciousness were significantly more frequent with SAH but did not occur in all cases. Location in the temporal region and pressing headache quality were the only features that were more common in non-SAH patients. Recurrent attacks of TCH occurred in 24% of the non-SAH patients. No SAH occurred later in this group, nor in any of the other patients. It was concluded that attacks caused by a SAH cannot be distinguished from non-SAH attacks on clinical grounds. It is important that patients with their first TCH attack are investigated with CT and CSF examination to exclude SAH, meningitis or cerebral infarction. The results from this and previous studies indicate that it is not necessary to perform angiography in patients with a TCH attack, provided that no symptoms or signs indicate a possible brain lesion and a CT scan and CSF examination have not indicated SAH.

Multiple sclerosis with and without CSF bands: Clinically indistinguishable but immunogenetically distinct

We sought to determine whether Swedish patients with multiple sclerosis (MS) with and without oligoclonal bands (OCBs) in the CSF constitute distinct subpopulations, clinically and immunogenetically. Our findings indicate that OCB-negative MS shares the same clinical features as OCB-positive MS regarding female predominance, age at onset, proportion of primary progressive cases, rate of MRI positivity, and disease severity. Our HLA-DRB1 genotyping results suggest, however, that OCB-positive and OCB-negative MS are immunogenetically distinct.

Age at onset of multiple sclerosis is correlated to use of combined oral contraceptives and childbirth before diagnosis

The aim of this study was to evaluate whether age of onset of multiple sclerosis is related to use of combined oral contraceptives and/or timing of childbirth. The results showed that use of combined oral contraceptives and childbirth before the first multiple sclerosis symptom was correlated to a higher mean age at the onset of the disease.

Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

Objective: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. Methods: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (C SF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in MS patients (11.6 mmol/L) compared with controls (7.4 mmol/L) (P =4-0.002). Seven patients showed low serum vitamin B12levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MC V), haemoglobin concentration, C SF tHcy or C SF MMA between patients and healthy subjects. There were no correlations between C SF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, C SF Hcy or C SF MMA were not correlated to disability status, activity of disease, duration of disease or age. Conclusions:The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. O ur findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. A nalysis of C SF MMA and C SF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.

Right-hemispheric brain activation correlates to language performance

Language function in the right-hemispheric homologues of Brocas and Wernickes areas does not only correlate with left-handedness or pathology, but occurs naturally in right-handed healthy subjects as well. In the current study, two non-invasive methods of assessing language lateralization are correlated with behavioral results in order to link hemispheric dominance to language ability in healthy subjects. Functional magnetic resonance imaging (fMRI) together with a sentence-completion paradigm was used to determine region-specific lateralization indices in the left- and right-sided Brocas and Wernickes areas, the frontal temporal lobe, the anterior cingulate cortex and the parietal lobe. In addition, dichotic listening results were used to determine overall language lateralization and to strengthen conclusions by correlating with fMRI indices. Results showed that fMRI lateralization in the superior parietal, the posterior temporal, and the anterior cingulate cortices correlated to dichotic listening. A decreased right ear advantage (REA), which indicates less left-hemispheric dominance in language, correlated with higher performance in most administered language tasks, including reading, language ability, fluency, and non-word discrimination. Furthermore, right hemispheric involvement in the posterior temporal lobe and the homologue of Brocas area suggests better performance in behavioral language tasks. This strongly indicates a supportive role of the right-hemispheric counterparts of Brocas and Wernickes areas in language performance.

Organic solvents and multiple sclerosis : A synthesis of the current evidence

To evaluate the possible relation between exposure to organic solvents and the development of multiple sclerosis, we carried out a best-evidence synthesis of the available information. We found 13 studies with varying methodology that included information on solvent exposure. In 10 of the studies, there were indications of an increased risk of multiple sclerosis in relation to solvent exposure. We made three selections of studies for both pooled analyses and meta-analyses. The relative risk point estimates that we obtained varied from 1.7 to 2.6. Our evaluation is consistent with the hypothesis that organic solvents may be a cause of multiple sclerosis.

Short‐term memory dysfunction in Kleine–Levin syndrome

Background – A previous investigation at our department of a young man with typical Kleine–Levin syndrome revealed short‐term memory dysfunction as well as hypoperfusion of the temporal lobes on single photon emission tomography (SPECT) (CERETECR) examination, 6 and 7 years after recovery, suggesting long lasting or even permanent cerebral dysfunction.

A case of Kleine–Levin syndrome examined with SPECT and neuropsychological testing

A case of Kleine–Levin syndrome with typical periodic hypersomnia and bulemia was diagnosed. On examination with single photo emission tomography (SPECT) (CERETEC®) during a relapse period and 2 weeks later there was marked cortical hypoperfusion of the frontal and temporal lobes, especially on the left side as well as in the right parietal lobe. Neuropsychological testing performed 1 week after a relapse showed a reduction in encoding to memory function of verbal learning indicating neocortical damage of the left fronto‐temporal region. A follow‐up 2 months later after the patient had spontaneously recovered showed only a slight left fronto‐temporal disturbance. CT and MRI of the brain were normal although the MRI showed a large and asymmetric mamillary body. Neuropsychological testing 6 years after recovery showed pronounced reduction in short‐time verbal and visual memory. Seven years after recovery SPECT demonstrated a normalized frontal perfusion but still a slight hypoperfusion in the left temporal lobe. Our results correlate to autopsy findings in two cases described previously.

Sensitivity to heat in MS patients: a factor strongly influencing symptomology - an explorative survey

BackgroundMany individuals diagnosed with Multiple Sclerosis (MS) are sensitive to increased body temperature, which has been recognized as correlating with the symptom of fatigue. The need to explore this association has been highlighted. The aim of this study was to investigate the occurrence of heat sensitivity and its relations to disease course, disability, common MS-related symptoms and ongoing immunosuppressive treatments among individuals 65 years of age or younger diagnosed with MS.MethodsA cross-sectional designed survey was undertaken. A questionnaire was sent to MS-patients with an Expanded Disability Status Score (EDSS) in the interval of 0-6.5 and who were between 20 and 65 years of age, living in an eastern region of Sweden (n = 334). Besides occurrence of heat sensitivity (Yes/No) and corresponding questions, the Fatigue Severity Scale (FSS), the MS-related symptom checklist and the Perceived Deficit Questionnaire (PDQ) were included. Data were analysed in relation to data level using Chi-square, Mann Whitney U-test, and Students t-test. Pearsons and Spearmans correlations were calculated. In the logistic regression analyses (enter) dichotomized MS-symptoms were used as dependent variables, and EDSS, disease-course, time since onset, heat-sensitivity, age and sex (female/male) were independent variables. In the linear regression analyses, enter, mean FSS and summarized PDQ were entered as dependent variables and EDSS, disease-course, time since onset, heat sensitivity, age and sex (female/male) were independent variables.ResultsOf the responding patients (n = 256), 58% reported heat sensitivity. The regression analyses revealed heat sensitivity as a significant factor relating not only to fatigue (p < 0.001), but also to several other common MS symptoms such as pain (p < 0.001), concentration difficulties (p < 0.001), and urination urgency (p = 0.009).ConclusionsHeat sensitivity in MS patients is a key symptom that is highly correlated with disabling symptoms such as fatigue, pain, concentration difficulty and urination urgency.

Sex ratio of multiple sclerosis in the National Swedish MS Register (SMSreg).

Background: Sex ratio in multiple sclerosis has been reported from several geographical areas. The disease is more common in women. In Europe the female-to-male ratio varies from 1.1 to 3.4. A recent study from Canada has reported a significant increase, with time, in female-to-male ratio in multiple sclerosis over the last 100 years. Objective: The aim of this study was to analyse any change in sex ratio in multiple sclerosis in the Swedish population. Methods: Data from the Swedish MS Register and data from the Swedish National Statistics Office were used to estimate sex ratio by year of birth and year of onset. Results: In the analysis of sex ratio by year of birth there were 8834 patients (6271 women and 2563 men) born between 1931 and 1985. The mean women-to-men ratio was 2.62. No clear trend was noted for the women-to-men ratio by year of birth (Spearman’s rho = 0.345, p = 0.298, n = 11). The number of patients analysed by year of onset was 9098 during the time period 1946 until 2005. The mean women-to-men ratio was 2.57. No significant change in women-to-men ratio (Spearman’s rho = −0.007, p = 0.983, n = 12) with time was observed. Conclusion: There is no evidence for an increasing women-to-men ratio with time amongst Swedish multiple sclerosis patients.