Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study.

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability. Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed. Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22-69) years with an Expanded Disability Status Score of 2 (0-8) and a disease duration of 11 (5-40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed. Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year. Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

Reliability of assessing lifestyle and trigger factors in patients with migraine--findings from the PAMINA study.

BACKGROUND AND PURPOSE: Numerous lifestyle factors are blamed for triggering migraine attacks. The reliability of assessing these factors retrospectively is unknown. Therefore, retrospective and prospective assessments of lifestyle in general and of migraine triggers in particular were compared in patients with migraine. METHODS: At baseline, the patients filled in two questionnaires covering the previous 90 days. Thereafter they kept a prospective 90-day diary. Questionnaires and diary included the same set of 45 factors. In the first questionnaire the patients assessed their lifestyle, in the second they rated for each factor the likelihood of triggering a migraine attack, and in the diary they recorded the daily presence of these factors irrespective of headache. Five categories were used for comparing frequencies in questionnaire and diary, defining agreement as identical categories in diary and questionnaire, minor disagreement and major disagreement as overestimation or underestimation by one category and two or more categories, respectively. RESULTS: In all, 327 patients (283 women, age 41.9 ± 12.1 years) who recorded 28,325 patient days were included. Calculating for each factor the percentage of patients with major disagreement the mean proportion was larger for trigger factors than for lifestyle (38.7% ± 6.6% vs. 16.9% ± 6.4%, P < 0.001). The proportion of factors showing major disagreement in more than 20% of the patients was 8.8% for lifestyle but 94.1% for trigger factors (P < 0.001). CONCLUSION: Comparing questionnaire and diary assessments of lifestyle and trigger factors in patients with migraine shows that questionnaire assessment of lifestyle is reliable, whereas trigger factors are overestimated and/or underestimated in retrospective questionnaires.

A longitudinal study on effects of a six-week course for energy conservation for multiple sclerosis patients.

OBJECTIVE: Fatigue management and energy conservation are effective strategies to minimize fatigue in multiple sclerosis (MS). Sustained results have not yet been reported. METHODS: A fatigue management course was provided for 32 MS patients. They were tested prior to, directly after participation in the course and in a 7-9 month follow-up with the Fatigue Severity Scale, the MS-specific Fatigue Scale, the Modified Fatigue Impact Scale (MFIS), the Pittsburgh Sleep Quality Index and a self-rating scale for depression. The Expanded Disability Status Score (EDSS) and the MS functional composite (MSFC) were evaluated before and after participation in the course. RESULTS: The total score and the Cognitive and Physical subscores of the MFIS showed significant improvements on both points of time. Scores in the Fatigue Severity Scale, MS-specific Fatigue Scale and Psychosocial Fatigue Impact Scale did not improve significantly. MS functional composite and EDSS remained unchanged after six weeks of course participation. Subjective sleep quality improved directly after participation in the course and after 7-9 months. The depression score decreased significantly to a normal level at the end of training and in the 7-9 month follow-up. CONCLUSION: Fatigue management enables MS patients to cope with their fatigue and energy more effectively. Follow-up evaluations showed stable results after 7-9 months.

Clinical features, classification and prognosis of migraine and tension-type headache in children and adolescents: a long-term follow-up study.

We performed a long-term follow-up examination in children and adolescents with migraine and tension-type headache (TTH) in order to investigate the evolution of clinical features and headache diagnoses, to compare International Classification of Headache Disorders (ICHD)-I and ICHD-II criteria and to identify prognostic factors. We re-examined 227 patients (52.4% female, age 17.6 +/- 3.1 years) 6.6 +/- 1.6 years after their first presentation to a headache centre using identical semistructured questionnaires. Of 140 patients initially diagnosed with migraine, 25.7% were headache free, 48.6% still had migraine and 25.7% had TTH at follow-up. Of 87 patients with TTH, 37.9% were headache free, 41.4% still had TTH and 20.7% had migraine. The number of subjects with definite migraine was higher in ICHD-II than in ICHD-I at baseline and at follow-up. The likelihood of a decrease in headache frequency decreased with a changing headache location at baseline (P < 0.0001), with the time between baseline and follow-up (P = 0.0019), and with an initial diagnosis of migraine (P = 0.014). Female gender and a longer time between headache onset and first examination tended to have an unfavourable impact. In conclusion, 30% of the children and adolescents presenting to a headache centre because of migraine or TTH become headache-free in the long-term. Another 20-25% shift from migraine to TTH or vice versa. ICHD-II criteria are superior to those of ICHD-I in identifying definite migraine in children and adolescents presenting to a headache centre. The prognosis is adversely affected by an initial diagnosis of migraine and by changing headache location, and it tends to be affected by an increasing time between headache onset and first presentation.

Facial pain in a neurological tertiary care centre--evaluation of the International Classification of Headache Disorders.

The aim of this study was to examine the diagnostic spectrum of facial pain and to evaluate the clinical features relevant to the differential diagnosis in a neurological tertiary care centre. This is the first investigation comparing the first with the second edition of the International Classification of Headache Disorders (ICHD-I, ICHD-II) in consecutively referred patients comprising a broad spectrum of disorders without restricting the inclusion to certain diagnoses. Studying 97 consecutive patients referred for facial pain, we found trigeminal neuralgia or other types of cranial neuralgia in 38% and 39% according to ICHD-I and ICHD-II, respectively; persistent idiopathic facial pain was diagnosed in 27% and 21%, respectively. The proportion of patients who could not be classified was 24% in ICHD-I and 29% in ICHD-II. Six per cent of the patients had cluster headache or chronic paroxysmal hemicrania, the remaining 5% had various other disorders. The agreement between ICHD-I and ICHD-II was very good to perfect. In ICHD-II, sensitivity and specificity were similar to ICHD-I, the specificity and negative predictive value were imrpoved in single features of trigeminal neuralgia, but were widely unchanged in persistent idiopathic facial pain. The number of patients who could not be classified was larger in ICHD-II than in ICHD-I. Modifying the diagnostic criteria for different types of facial pain, in particular changes in the criteria of persistent idiopathic facial pain, might be helpful in reducing the number of patients with unclassifiable facial pain.

Clinical features of migraine: a cross-sectional study in patients aged three to sixty-nine.

We investigated 260 consecutive patients classified as migraine cases aged 3-69 at two tertiary headache centres, one for children and adolescents and the other for adults to evaluate the relationship between age and clinical features of migraine cross-sectionally. We only included subjects with definite migraine without or with aura and we excluded subjects with coexisting tension-type headache, medication overuse and/or other clinically relevant disorders. The percentage of males decreased markedly from childhood to adulthood and this affected the evaluation of age-related changes in male patients, as only large differences reached the level of statistical significance. In females, the headache duration and the prevalence of unilateral, pulsating pain, photophobia and phonophobia increased, whereas the prevalence of aggravation by physical activity decreased with age. In conclusion, this cross-sectional, clinic-based study on a strictly defined sample of 260 consecutive patients with definite migraine covering a wide range of age from the very young to the old suggests marked age-related differences of the clinical features of migraine in females and failed to demonstrate similar differences in males due to the small number of adult male migraineurs.

Migrainous disorder and headache of the tension-type not fulfilling the criteria: a follow-up study in children and adolescents.

In this follow-up study in children and adolescents with recurrent headaches classified as migrainous disorder (IHS 1.7) and headache of the tension-type not fulfilling the criteria (IHS 2.3), 28.6% were headache-free and 71.4% still had headaches 2-5 years after the first examination. The majority remained in the same one-digit IHS diagnosis, whereas 20% changed from migraine to tension-type headache or vice versa. The number of IHS criteria fulfilled increased significantly from the first to the second examination. The reason for diagnosing IHS 1.7 and IHS 2.3 most often was a short headache duration or headache characteristics not meeting the criteria. By reducing the minimum headache duration to 1 h, 11 of 58 patients could be diagnosed as migraine without aura. There was a remarkable overlap in the diagnostic criteria for migraine without aura and tension-type headache. In IHS 1.7 and IHS 2.3 this overlap exceeded 80%, with a trend to decrease at the second examination.

Vaccinations and steroids in MS: effects on disease progression and mood.

OBJECTIVE: To investigate the effects of vaccinations and steroids on disease progression and mood in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Twenty-three patients with clinically definite MS were questioned with respect to vaccination history and the cumulative dose of steroids given during their life-time. EDSS scores and MRI scans of the brain were obtained and used to quantify clinical and MRI disease progression. Mood was assessed by using a self-estimated adjective mood scale. RESULTS: The number of vaccinations showed no effect on disease progression or mood. High cumulative steroid doses were associated with rapid MRI disease progression and the number of supratentorial MRI lesions. The absence of band-like MRI lesions was correlated with rapid clinical and MRI disease progression. Self-estimated mood tended to be worse in patients with chronic-progressive MS compared to those with relapsing-remitting MS. CONCLUSION: Neither clinical nor MRI-documented disease progression nor mood are influenced by the total number of vaccinations whereas high cumulative steroid doses and the absence of band-like MRI lesions indicate rapidly progressive MS. Self-estimated mood tends to be worse in patients with chronic-progressive MS compared to patients with relapsing-remitting MS.

Posturographic findings in patients with idiopathic cervical dystonia before and after local injections with botulinum toxin.

In this posturographic study, whole-body postural control was impaired in more than 75% of patients with idiopathic cervical dystonia (ICD) before local injections with botulinum toxin type A (BTX-A) and the impairment was independent of the direction of the torticollis. Six weeks after therapy with BTX-A, the number of pathological posturographic parameters had decreased by almost 30%, and the improvement reached statistical significance for sway path, sway area and anteroposterior sway during stance on foam with eyes closed. From a pathophysiological point of view, this improvement may be explained - at least in part - by a reduction of abnormal proprioceptive input from the neck. Accordingly, it seems possible that neck proprioceptive input plays a role in whole-body postural control in ICD patients, even though previous studies suggested that the neck input is relatively ignored in these patients.

[Neurological and psychosocial sequelae 4 and 8 years after severe craniocerebral injury: a catamnestic study]. / Neurologische und psychosoziale Folgen 4 und 8 Jahre nach schwerer Schädelhirnverletzung: eine katamnestische Studie.

Thirty-three patients (29 male, 4 male) were examined 4 and 8 years after severe head injury. The patients underwent a detailed neurological examination. A semistructured interview according to the Glasgow Assessment Schedule was administered to the patients and their relatives. Most frequent neurological features were motor deficits (55%, at both follow-up investigations, mostly monoparesis), dysarthria (39% versus 33%), ataxia (49% versus 39%) and anosmia (46% versus 33%) at 4 and 8 years, respectively. There was a slight, but not significant improvement between the 2 examinations with respect to frequency and severity of neurological impairment. There was no significant improvement in the activities of daily living and 18% remained totally dependent on other people's help. At both follow-ups 85% complained of memory deficits. 67% and 70% respectively, suffered from poor initiative and increasing irritability at the first and second examination. The patients were more socially isolated and more irritable at the second follow-up. Only 12% and 18%, respectively held the same job as they had had before the injury; nearly half of them had retired. Occupational and psychosocial reintegration appeared to be rather poor in many patients. Excessive alcohol intake prior to trauma was identified as a person-related predictive factor. In contrast to other studies we found persistent, although slight neurological deficits. In the long-term, a combination of neurological and neuropsychological deficits seems to contribute to residual handicap.

Psychosocial long-term outcome of severe head injury as perceived by patients, relatives, and professionals.

OBJECTIVE: We systematically compared information on psychosocial outcome of severe head injury (SHI) gathered from different informants. MATERIAL AND METHODS: We evaluated psychosocial outcome in 33 subjects 8.1 +/- 1.4 years after having suffered SHI using data gathered from the patients themselves, caring relatives, and an assessing neurologist. RESULTS: Our data confirm long-lasting negative effects of SHI on psychosocial functioning even in patients with only mild or moderate neurological impairment. Specific problems in social intercourse, stemming from impaired self-control, are regularly reported by the relatives and probably underestimated by the patients and by the doctors. In contrast, we found a remarkable agreement between self-report and professional estimation in other aspects of psychological consequences of SHI such as depressed mood and social withdrawal. CONCLUSIONS: Our results challenge the common view that patients having suffered from severe SHI are altogether unreliable informants. However, SHI patients tend to have difficulties in monitoring their specific problems of control of behaviour in social relationships. Therefore information gathered from the caring relatives should always be included when evaluating psychosocial sequels of severe SHI.

IHS criteria and gender: a study on migraine and tension-type headache in children and adolescents.

The aim of this study was to investigate whether the IHS criteria for migraine and tension-type headache depend on gender. Among 409 children and adolescents with recurrent idiopathic headache seen at a university outpatient clinic, girls had significantly more often migraine with aura. Also, there was a trend towards a higher frequency of tension-type headache in girls. In migraine, aggravation of headache by physical activity and occurrence of aura symptoms were more common in females, whereas vomiting and phonophobia occurred more often in males. In tension-type headache, females more often reported mild intensity of headache. All other criteria were similar in both sexes. Age influenced the expression of some of the accompanying symptoms in the various types of migraine, but had only minimal influence on other diagnostic criteria of migraine and tension-type headache in females as well as in males. Our study suggests that the frequency of migraine (except that of migraine with aura) is similar among girls and boys, that tension-type headache may occur more often in girls, and that gender has some influence on the IHS criteria for migraine, but almost no influence on those of tension-type headache.

Magnetic resonance imaging for recurrent headache in childhood and adolescence.

We investigated 429 consecutive patients, aged 5 to 18 (mean: 11.0 +/- 3.1) years, diagnosed with migraine or tension-type headache. The patients underwent either MRI or exclusively clinical follow-up examinations. Magnetic resonance imaging revealed normal findings in 82.3% and structural changes in 17.7%. However, the vast majority of these changes had minimal or no pathological relevance, and a causal relationship to the patient's headache could not be proven in any case. In the non-MRI group, clinical follow-up examinations confirmed the initial diagnosis in all patients and MRI was not required in any of these subjects. In conclusion, our study shows a poor relation between recurrent headache fulfilling the criteria of migraine and tension-type headache and structural changes incidentally detected by MRI. In addition, it suggests that clinical follow-up examinations are reliable. Accordingly, MRI is not required for routine examination of recurrent headache in children and adolescents, but it should be performed in patients with abnormal neurological findings, atypical headache pattern, or significant change of preexisting headache.

Diagnosis of headache in childhood and adolescence: a study in 437 patients.

We investigated whether the criteria for idiopathic headache published by the International Headache Society (IHS) are useful in childhood and adolescence and compared the diagnoses according to this classification with those of Vahlquist. We used a semi-structured questionnaire to examine a total of 437 children and adolescents referred consecutively to a headache outpatient clinic. Twenty-eight of 437 patients were excluded because of symptomatic or unclassifiable headache. Of 409 patients with idiopathic headache, 70.4% had definite migraine or tension-type headache (IHS 1.1, 1.2, 2.1, 2.2), 20.5% had a migrainous disorder (IHS 1.7) and 9.1% had headache of the tension-type not fulfilling the criteria (IHS 2.3). In the differential diagnosis of migraine and tension-type headache the intensity of pain, aggravation of headache by physical activity, nausea and vomiting were the most important features. The quality of pain, photo- and phonophobia were less helpful and location least important. The duration of migraine attacks was less than 2 h in 19.0% of the migraine patients. In general, the diagnostic criteria of migraine were highly specific but less sensitive, and those of tension-type headache highly sensitive but less specific. The agreement between IHS criteria and those of Vahlquist was marked (kappa = 0.57). We conclude that the IHS criteria are useful for classifying headache in children and adolescents referred to a headache outpatient clinic. A forthcoming modification of the IHS criteria should consider a reduction of the minimum duration of migraine attacks from 2 h to 1 h and should try to increase the sensitivity of the criteria for migraine and the specificity of the criteria for tension-type headache.