Progressive multifocal leukoencephalopathy or immune reconstitution inflammatory syndrome after fingolimod cessation? A case report.

BACKGROUND: Fingolimod is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML); however, its discontinuation may cause severe immune reconstitution inflammatory syndrome (IRIS). As both of these conditions (especially fingolimod induced PML) are rarely described in medical case reports distinguishing between PML-IRIS and MS-IRIS may be diagnostically challenging. CASE PRESENTATION: We report a patient with severe clinical decline (Expanded Disability Status Scale (EDSS) increasing from 3.5 to 7.5) and multiple, large, contrast-enhancing lesions on brain magnetic resonance imaging (MRI) a few months after fingolimod withdrawal. The diagnostic possibilities included IRIS due to fingolimod withdrawal versus PML-IRIS. The JC virus (JCV) antibody index was positive (2.56); however, cerebrospinal fluid (CSF) JCV real-time polymerase chain reaction (JCV-PCR) was negative and brain biopsy was not performed. After a long course of aggressive treatment (several pulsed methylprednisolone infusions, plasmapheresis, intravenous dexamethasone, oral mirtazapine) the patient gradually recovered (EDSS 2.5) and MRI lesions decreased. CONCLUSIONS: This case report demonstrates the importance of monitoring patients carefully after the discontinuation of fingolimod for PML-IRIS and rebound MS with IRIS as these conditions may manifest similarly.

EVALUATION OF BILATERAL ASYMMETRY BETWEEN UPPER LIMB MASSES IN RIGHT-HANDED YOUNG ADULTS OF BOTH SEXES.

The study introduced a novel precise method for measurement and calculation of upper arm mass and to assess the difference between masses of upper limbs on the dominant and non-dominant sides of the body of right-handed participants. Forty healthy untrained male (n = 20; M age = 20.8 yr., SD = 1.2) and female (n = 20; M age = 20.7 yr., SD = 1.3) participants without a history of upper-extremity pathology participated. Kinematic and kinetic data were collected during arm motion. The mass of each arm was calculated. Each participant performed 20 movements with each arm. Most often the dominant arm was more massive than the non-dominant in both sex groups; however, mass was more symmetric for female participants than for male participants. Regression equations related to total body mass were calculated for each arm independently.

Influence of spatial accuracy constraints on reaction time and maximum speed of performance of unilateral movements.

The goal was to study reaction time and maximal velocity of upper limbs of healthy young adults of both sexes during transition from a simple to a more involved task. Performance of dominant and non-dominant arms was recorded. Participants were 43 healthy, right-handed, untrained men (n=22) and women (n=21), 18-22 years old. The simple task required a single jerk-like movement. The involved task required both speed and accuracy where necessity for high speed of performance was emphasized. The effectiveness of transition between tasks was calculated for both reaction time and maximal velocity. No lateral differences were found. Men usually had a shorter reaction time on both tasks and a higher maximal velocity in the simple task. Women were more effective at modifying velocity.

Age-related changes in force and power associated with balance of women in quiet bilateral stance on a firm surface.

Quantitative assessment of the fluctuations of the body centre of mass (CM) while in a stationary bilateral stance on a firm surface is an important criterion of the functional state of human motor-vestibular and sensory apparatus. From analysis of the literature we conclude that more objective characteristics of human balance in quiet standing may be the amount of energy used to maintain the CM in a constant position. Further analysis of the references showed that these characteristics have not been investigated in neurological practice. In this study, the displacement of CM in participants standing in a normal anatomical position was analysed. Forty-five healthy women in three age groups: 18-24, 45-55 and over 60 years participated in the experiments, which consisted of recording changes in partial body weight on the force platform (under one leg) in situations with opened and closed eyes. The specific power of oscillation of body sway and force of lateral swing of CM were calculated. Results indicated that the maximum specific power of oscillation and force of lateral swing were observed in the group of women older than 60 years, especially in the absence of vision. Minimum values occurred in the group of 18-24 years. We also found a considerable variability in all indices in all age groups. This indicates that the stability of the vertical posture in humans depends also on the individual biological characteristics of the central nervous and muscular systems.

Behavior of dominant and non dominant hands during ballistic protractive target-directed movements.

The purpose of this study is to investigate the asymmetry of dominant and non-dominant arms regarding reaction time (RT), velocity, force and power generated during ballistic target-directed movements. Fifty six, right-handed young males performed protractile movements with both arms separately by pushing a joystick towards a target-line as quickly and as accurately as possible. Participants performed 21 repetitions with each hand. The temporal, spatial, kinetic and kinematic parameters were computed. All movements were grouped regarding their accuracy (when joystick fell short, stopped precisely or overreached the target). Each group of movements was analyzed separately and the data obtained was compared across groups. The results showed that although the left arm was less accurate than the right one, it reached the target significantly faster, developing greater average force and power. The forces of acceleration and deceleration of the left arm were greater too. We did not observe a significant lateral difference in RT in situations when the arm fell short of the target, or stopped precisely on the target. It was only when the target was overreached that the left arm displayed a significantly greater RT than the right one. We explain the results from the asymmetry of motor behavior in favor of the influence of both hemispheres in this process.

Relationship between simple reaction time and body mass index.

The aim was to establish the relationship between simple reaction time in motor response in young adults in relation to their body physique, as represented by body mass index. Forty-five young male participants were allocated to one of three anthropometric groups, based on their body mass index. Participants performed 100 reaction-time trials with instructions to move a joystick, as quickly as possible, as soon as they detected a single star appearing in the centre of a monitor. All data were statistically selected into seven intervals and data from the mode frequency interval were precisely analysed. Participants from the group with greater body mass index reacted significantly slower than others. We did not record group lateral differences based on simple reaction time in each selected group. We recommend for future researchers the importance of identification of the level of body mass index of participants prior to testing them for effectiveness of simple sensori-motor reactions.

Headache after concussion.

BACKGROUND AND PURPOSE: Chronic post-traumatic headache attributed to mild head injury is a somewhat disputed headache diagnosis. A main object of this study was to assess the validity of this diagnosis by studying the headache pattern of concussed patients that participated in one historic (n = 131) and one prospective cohort (n = 217) study. METHODS: Head injury patients were recruited from two hospitals in Kaunas, Lithuania. Controls were recruited amongst patients with minor orthopaedic traumas not involving the head and neck. RESULTS: When data from the two studies were pooled, no difference in any headache category (diagnosis, attack frequency, symptoms) was found one or more years after the trauma, except that photophobia was somewhat more prevalent amongst the concussed patients. In both injury groups, the existence of pre-traumatic headache was a predictor of post-traumatic headache, although pre-traumatic headache seems to have been underreported amongst the concussed patients. There was a significant negative correlation between the duration of unconsciousness and the headache. CONCLUSIONS: This negative correlation, and the lack of specificity indicates that headache occurring 3 months or more after concussion is not caused by the head or brain injury. Rather it may represent an episode of one of the primary headaches, possibly induced by the stress of the situation.

Examination of the diagnostic validity of 'headache attributed to whiplash injury': a controlled, prospective study.

Acute and chronic headache attributed to whiplash injury are new diagnostic entities in the International Classification of Headache Disorders, second edition. A main objective of the present study was to assess the validity of these nosologic entities by studying the headache pattern in an inception cohort of 210 rear-end car collision victims and in 210 matched controls. Consecutive drivers involved in rear-end collisions were identified from the daily records of the Traffic Police Department of Kaunas, Lithuania. A standard self-report questionnaire was sent to the drivers between 2 and 7 days after the collision, and their passengers were recruited as well. Headache and neck pain were evaluated within 7 days of the collision, at 2 months and 1 year after the collision. A control group of non-traumatized subjects received questionnaires at the time of the selection and 1 year later. Of the 75 collision victims who developed headache within the first 7 days of the collision, 37 had a clinical picture in accordance with the criteria for acute whiplash headache (i.e., concomitant neck pain) and 38 did not. For acute headache after collision, concomitant neck pain was of no relevance to the headache type or its course. In both these subgroups, migraine and tension-type headache could be diagnosed in similar proportions and the prognosis after 2 months and 1 year was also similar. Preexisting headache was a strong prognostic factor in both groups for both acute and chronic pain. Compared with the non-traumatized control group, the 1-year incidence of new or worsened headache, or of headache improvement, was the same. A likely interpretation of the data is that acute headaches after rear-end car collisions mainly represent episodes of a primary headache precipitated by the stress of the situation. We conclude that the nosologic validity of both acute and chronic whiplash headache is poor as the headaches, in accordance with the criteria lack distinguishing clinical features and have the same prognosis compared with headaches in a control group.

Effect of age on metabolic fatigue and on indirect symptoms of skeletal muscle damage after stretch-shortening exercise.

AIM: The purpose of this study was to establish the main differences between men (M) and adolescents (A) (males) in metabolic fatigue and damage induced by exercise performed at maximal intensity. METHODS: Healthy A (age 13.4 0.6 years, n = 12) and healthy adult M (age 25.4 1.7 years, n = 12) participated in this study. To induce muscle damage and metabolic fatigue stretch-shortening exercise (SSE) (5 bouts of 20 jumps with counter-movement to 90 degrees angle in the knee with 10 s between bouts) has been chosen. The following data were measured: the force of the quadriceps muscle, aroused by electrical stimulation at different frequencies, maximal voluntary contraction force, height of jump (JH), muscle soreness, lactate (La) concentration and creatine kinase (CK) activity in the blood. All the parameters mentioned were measured before exercise and 2-5 min, 20 min, 24 h and 48 h after the SSE, except for La concentration changes in the blood measured before exercise, 2 min and 20 min after the SSE. RESULTS: The main findings in this study are the following: 1) during SSE JH decreased significantly (P < 0.05) more in M than in A, whereas La concentration in the blood after SSE increased more in M than in A; 2) indirect symptoms of muscle damage were more evident in M than in A; 3) there was secondary decrease in electrically induced muscle force at 10-20 Hz from 3 min until 20 min after SSE but only in the muscles of M; 4) low frequency fatigue after SSE was more evident in M than A. CONCLUSIONS: The results of the present study indicate that the muscles of adolescents are more resistant to both metabolic fatigue and exercise-induced damage than those of men.

A controlled prospective inception cohort study on the post-concussion syndrome outside the medicolegal context.

In an earlier historical cohort study on the post-concussion syndrome (PCS) in Lithuania, a country in which there are few confounding factors, the validity of this condition as a disease entity could not be confirmed. In order to register the post-traumatic symptoms, the influence of sociodemographic factors, and the effect of expectation on these symptoms more reliably, we performed a controlled prospective study. Three hundred subjects with concussion were followed up with repeated questionnaires for 1 year. For each study subject, a sex- and age-matched control person with minor non-head injury was identified. These controls received similar questionnaires. Headache both after 3 months and after 1 year did not differ significantly between the head-injured participants and the non-head-injured controls. Several other symptoms attributed to PCS did not differ significantly between the groups after 3 months. After 1 year the vast majority of symptoms did not differ significantly. Exceptions were slightly significant differences concerning memory problems, concentration problems, dizziness and tiredness. These differences were insignificant when analysing symptoms in unmarried and/or people with lower education, separately. No relationship between cognitive dysfunction and the severity of concussion was found. Although the possibility of a mild organic brain injury cannot be completely ruled out, our results cast doubt on the validity of PCS as a useful clinical entity, at least for head injuries with loss of consciousness for <15 min. Sociodemographic factors and expectation seem to influence reporting of symptoms after concussion.

A controlled historical cohort study on the post-concussion syndrome.

In Lithuania, expectation of chronic symptoms after minor head injury is less than in western countries and possibilities for monetary compensation are minimal. Therefore, an opportunity exists to study the post-concussion syndrome (PCS) without several confounding factors present in western societies. We sent questionnaires about symptoms attributed to PCS to 200 subjects who had a concussion with loss of consciousness between 35 and 22 months before the study. For each study subject, a sex- and age-matched control person with minor non-head injury was identified. These controls received similar questionnaires. All the responding post-concussion patients stated that they had had acute headache after the trauma but this headache had disappeared in 96% of cases within 1 month. Headache and dizziness at the time of the questioning were not significantly more prevalent in the patients with concussion than in the controls, and there was no significant difference concerning subjective cognitive dysfunction. Scores of visual analogue scales of symptoms attributed to PCS showed no significant differences except for depression, alcohol intolerance and worry about brain injury, which were more frequent in the concussion group. No specific effect of the head injury was detected when various definitions and different constellations of core symptoms of PCS were used. These findings question the validity of the PCS as a useful clinical entity.

Natural evolution of late whiplash syndrome outside the medicolegal context.

BACKGROUND: In Lithuania, few car drivers and passengers are covered by insurance and there is little awareness among the general public about the potentially disabling consequences of a whiplash injury. We took this opportunity to study the natural course of head and neck symptoms after rear-end car collisions. METHODS: In a retrospective questionnaire-based cohort study, 202 individuals (157 men; 45 women) were identified from the records of the traffic police department in Kaunas, Lithuania. These individuals were interviewed 1-3 years after experiencing a rear-end car collision. Neck pain, headache, subjective cognitive dysfunction, psychological disorders, and low back pain in this group were compared with the same complaints in a sex-matched and age-matched control group of uninjured individuals selected randomly from the population register of the same geographic area. FINDINGS: Neck pain was reported by 71 (35% [95% CI 29-42]) accident victims and 67 (33% [27-40]) controls. Headache was reported by 107 (53% [46-60]) accident victims and 100 (50% [42-57]) controls. Chronic neck pain and chronic headache (more than 7 days per month) were also reported in similar proportions (17 [8.4%; 5-13] vs 14 [6.9%; 4-12] and 19 [9.4%; 6-15] vs 12 [5.9%; 3-10]) by the two groups. Of those who reported chronic neck pain or daily headache after the accident, substantial proportions had had similar symptoms before the accident (7/17 for chronic neck pain; 10/12 for daily headache). There was no significant difference found. No one in the study group had disabling or persistent symptoms as a result of the car accident. There was no relation between the impact severity and degree of pain. A family history of neck pain was the most important risk factor for current neck symptoms in logistic regression analyses. INTERPRETATION: Our results suggest that chronic symptoms were not usually caused by the car accident. Expectation of disability, a family history, and attribution of pre-existing symptoms to the trauma may be more important determinants for the evolution of the late whiplash syndrome.