Caroline I.E. Renner

Structured Assessment of Hypopituitarism after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage in 1242 Patients: The German Interdisciplinary Database

Clinical studies have demonstrated that traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) are frequent causes of long-term disturbances of hypothalamo-pituitary function. This study aimed to assess the prevalence and associated factors of post-traumatic hypopituitarism in a large national registry of patients with TBI and SAH. Data were collected from 14 centers in Germany and Austria treating patients for TBI or SAH and performing endocrine assessments. Data were collected using a structured, internet-based study sheet, obtaining information on clinical, radiological, and hormonal parameters. A total of 1242 patients (825 TBI, age 43.5±19.7 years; 417 SAH, age 49.7±11.8 years) were included. We studied the prevalence of hypopituitarism reported based on different definitions of laboratory values and stimulation tests. Stimulation tests for the corticotropic and somatotropic axes were performed in 26% and 22% of the patients, respectively. The prevalence of hypopituitarism in the chronic phase (at least 5 months after the event) by laboratory values, physician diagnoses, and stimulation tests, was 35%, 36%, and 70%, respectively. Hypopituitarism was less common in the acute phase. According to the frequency of endocrine dysfunction, pituitary hormone secretion was impaired in the following sequence: ACTH, LH/FSH, GH, and TSH. TBI patients with abnormal stimulation tests had suffered from more severe TBI than patients with normal stimulation tests. In conclusion, our data confirm that hypopituitarism is a common complication of TBI and SAH. It is possible that patients with a higher likelihood of hypopituitarism were selected for endocrine stimulation tests.

Change of facilitation during voluntary bilateral hand activation after stroke

BACKGROUND AND PURPOSE The relearning of daily activities after stroke also involves performance of bimanual tasks. This raises the possibility that concurrent activation of the healthy hemisphere interferes with reorganization processes in the affected hemisphere due to inhibitory pathways between homologous motor cortex representations. This study investigated the effect of voluntary, simultaneous activation of both hands upon the non-dominant (healthy subjects) or affected (stroke patients) hemisphere. METHODS Eleven healthy subjects and 16 stroke patients were investigated using transcranial stimulation (TMS). TMS was applied over the non-dominant/affected hemisphere during performance of an isometric pinch grip at different force levels (10% or 50% of maximal voluntary contraction) with the contralateral hand. The ipsilateral hand had to perform the pinch grip at various force levels (10%, 50%, or 100% of maximal voluntary contraction) simultaneously. Peak-to-peak amplitudes of motor evoked potentials (MEPs) were compared to assess differences in motor cortex excitability. RESULTS Unilateral activity of either hand alone exerted a facilitatory effect upon the non-dominant or affected hemisphere. In healthy subjects, the activation of the ipsilateral hand simultaneously with the contralateral hand did not produce any significant change of the MEP amplitudes compared to unilateral activation of the contralateral hand. In patients, however, the additional activation of the ipsilateral hand caused an additional increase of the peak-to-peak amplitudes. CONCLUSION In healthy subjects voluntary activation of the ipsilateral hand does not change the excitability of the motor cortex of the non-dominant hemisphere, when the contralateral hand is simultaneously activated. The facilitation of the contralateral hand seems to gate further facilitation by the ipsilateral hand. However, in stroke patients simultaneous activation of both hands causes an additional facilitation compared to activation of the affected hand alone.

Enhanced Motor Cortex Excitability During Ipsilateral Voluntary Hand Activation in Healthy Subjects and Stroke Patients

Background and Purpose— It is still a matter of debate whether the ipsilateral voluntary hand activation has a facilitatory or inhibitory effect on the nondominant or affected hemisphere. To give an answer to this question is of great importance for the rehabilitation of stroke patients, because they often use the unaffected hand for compensation. Methods— Ten healthy volunteers and 11 stroke patients were investigated using transcranial magnetic stimulation (TMS). TMS was applied to the dominant/unaffected hemisphere during performance of different tasks (simple index finger abduction, pinch grip, and power grip) at various force levels (5%, 10%, 50%, and 100% maximal voluntary contraction) with the ipsilateral hand. Peak-to-peak amplitudes of motor-evoked potentials were used as measure for motor cortex excitability. Results— Both simple and complex tasks led to a facilitation of the contralateral corticospinal system at all levels of applied force. Not only the facilitatory effect in general but also the slope of the relationship between force level and MEP amplitude were significantly lower in stroke patients indicating that both the general activation level of the impaired motor system and the bandwidth of possible activation levels are diminished. Conclusion— Voluntary activation of the hand does not exert an inhibitory effect on the excitability of the ipsilateral hemisphere in healthy volunteers or in stroke patients.

The influence of gender on the injury severity, course and outcome of traumatic brain injury

Objective: To examine the independent association of gender with injury severity, clinical course, pituitary dysfunction and outcome after traumatic brain injury (TBI). Design: Prospective cohort, analysis of a data sub-set collected as part of the nation-wide database ‘The Structured Data Assessment of Hypopituitarism after TBI and SAH’. Methods and procedures: Four hundred and twenty-seven patients following TBI were observed from acute care through neurological rehabilitation. Outcome was measured by Glasgow Outcome Scale (GOS), employment status and living situation post-injury. As a secondary outcome measure anterior pituitary function was assessed. Results: There were no differences in injury severity between men and women. Age had a significant effect on the GCS score (p = 0.0295), but gender did not (p = 0.4105). The outcome was equivalent between men and women once corrected for age. Logistic regression revealed that gender had no effect (p = 0.8008), but age (p = 0.0021) and initial injury severity (p = 0.0010) had an effect on the GOS. After correcting for pre-injury living situation and employment only initial injury severity (p = 0.0005) influenced GOS. Pituitary insufficiency was not affected by sex or age. Conclusion: Gender does not seem to influence the course and outcome of TBI. Outcome parameters were affected foremost by initial injury severity and by age, but not by sex.

Change of Strength and Rate of Rise of Tension Relate to Functional Arm Recovery After Stroke

OBJECTIVE To examine the relationship between individual strength parameters and functional motor ability over time during rehabilitation in stroke patients. DESIGN A multiple-baseline experiment with assessment at inclusion and after 3 and 6 weeks. SETTING Secondary-care rehabilitation center. PARTICIPANTS A convenience sample of 16 subacute stroke patients. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Maximal voluntary force and rate of rise of tension of hand grip, wrist extension, and elbow flexion and extension were recorded at all 3 times. At the same time, functional motor assessments were evaluated by the Action Research Arm Test (ARAT), Box and Block test, and Rivermead Test. RESULTS We found no correlation between maximal voluntary force increases of various muscle contractions measurements. Neither the increase of grip strength nor that of wrist extension force correlated with improvement in ARAT score. Yet the improvement in the rate of rise of tension of hand grip (Spearman rho=.91) and of wrist extension (Spearman rho=.73) correlated with the improvement of the ARAT score and explained 77% of the variance of the ARAT. CONCLUSIONS The change in the rate of rise of tension of the hand grip has a better predictive value for the functional recovery compared to the change in maximal voluntary force in patients with moderate arm and hand weakness after stroke. The rate of rise of tension of hand grip seems an adequate quantifiable parameter to detect small improvements during functional recovery.

Central Compensation at Short Muscle Range Is Differentially Affected in Cortical Versus Subcortical Strokes

Background and Purpose— The active force generated by a single muscle fiber is greatest in midrange. In healthy subjects, the reduced muscle force at short muscle length is partially compensated by modified patterns of muscle activation, probably central in origin. These patterns are presumed to be deficient after stroke. We examined the excitability muscle-length relation in stroke patients and healthy controls and hypothesized about its alteration in stroke patients. Methods— Corticospinal excitability was assessed in 31 stroke patients (19 subcortical, 12 cortical) and 19 healthy volunteers by transcranial magnetic stimulation. We recorded the motor evoked potentials (MEPs) simultaneously from the biceps brachii and the triceps brachii muscles at 0°, 20°, 40°, 60°, 80°, 100°, and 120° degrees of elbow flexion (0° being full elbow extension). Results— Normal subjects revealed a significant increase in MEP amplitudes at shortened muscle lengths for both the flexor and extensor muscles (P<0.001). Multivariate variance analysis revealed that the MEP-angle curves of cortical stroke patients were significantly different from those of the control group for both muscles, lacking an increase of corticospinal excitability at short muscle length. Yet the MEP-angle curves for the subcortical stroke patients did not show a statistically significant difference from the control group for either muscle. Conclusion— Cortical and subcortical strokes differentially affect the corticospinal excitability muscle-length relation. This may account for the reported disproportionate decrease in muscle strength at shortened range after stroke.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

Intracortical excitability after repetitive hand movements is differentially affected in cortical versus subcortical strokes.

Repetitive training of isolated movements induces reorganization of motor cortical representations. To elucidate the mechanisms of practice-dependent cortical plasticity within the lesioned central motor system at the time of the application of a therapeutic intervention, we examined the effect of repetitive movements on intracortical facilitation (ICF) and inhibition of agonist (extensor carpi radialis [ECR]) and antagonist (flexor carpi ulnaris) muscles of the hand shortly after the movements, by the paired-pulse technique in patients with cortical (n = 9) and subcortical strokes (n = 11). Short intracortical inhibition and ICF were studied by using interstimulus intervals of 2 and 8 milliseconds, respectively, and their interaction with active or passive movement. The active movement produced significantly larger motor-evoked potentials in the ECR muscle in both patient groups. Short intracortical inhibition was particularly decreased after cortical stroke, whereas it was still significant after subcortical stroke. ICF increased significantly after movements compared with rest in the ECR for subcortical stroke patients only. We conclude that repetitive active movements increase the excitability of the motor cortex representing the agonist muscle and interact with intracortical facilitatory circuits in the subcortical stroke group but not in the cortical stroke group. This interaction of circuitry has been reported previously in control subjects and seems to still operate after subcortical stroke during active movement. Alternative networks may be recruited for active movement after cortical stroke. This finding proposes lesion-specific mechanisms of reorganization during the same rehabilitative intervention. Distinct rehabilitative strategies may be required to optimize the activation of the physiologic motor network for different lesions.

Selective effect of repetitive hand movements on intracortical excitability

Repetitive training of isolated movements induces local reorganization of the motor cortex. To investigate the effect of repetitive movements on intracortical inhibition and facilitation shortly after the movements, we performed paired‐pulse transcranial magnetic stimulation in 12 healthy subjects by using interstimulus intervals of 2 and 8 ms, respectively. Motor evoked potentials (MEPs) were recorded simultaneously from the extensor carpi radialis (ECR) and the flexor carpi ulnaris muscle (FCU) following paired stimuli at rest or 1 s after repetitive (every 6 s) active or passive wrist extensions and compared with MEPs produced by single stimuli at rest. The active movements produced significantly larger MEPs in the ECR but not the FCU muscle. Passive movements had no effect. Intracortical facilitation increased significantly after movements in the ECR only. Intracortical inhibition, however, did not change significantly after repetitive movements in either muscle. These findings support the notion that intracortical inhibition and facilitation may be controlled independently. Further, these data suggest that shortly after repetitive movements the excitability of the primary motor cortex representing the agonist muscle is increased by interaction with intracortical facilitatory circuits rather than by inactivating inhibitory circuits. Muscle Nerve, 2005

Group therapy task training versus individual task training during inpatient stroke rehabilitation: a randomised controlled trial

Objective: To compare the efficacy of intensive daily applied progressive group therapy task training with equally dosed individual progressive task training on self-reported mobility for patients with moderate to severe stroke during inpatient rehabilitation. Design: Randomized controlled clinical trial. Setting: In-patient rehabilitation center. Subjects: A total of 73 subacute patients with stroke who were not able to walk without physical assistance at randomisation. Interventions: Patients were allocated to group therapy task training (GT) or individual task training (IT). Both interventions were intended to improve walking competency and comprised 30 sessions of 90 minutes over six weeks. Main measures: Primary outcome was the mobility domain of the Stroke Impact Scale (SIS-3.0). Secondary outcomes were the other domains of SIS-3.0, standing balance, gait speed, walking distance, stair climbing, fatigue, anxiety and depression. Results: No adverse events were reported in either arm of the trial. There were no significant differences between groups for the SIS mobility domain at the end of the intervention (Z= −0.26, P = 0.79). No significant differences between groups were found in gait speed improvements (GT:0.38 ±0.23; IT:0.26±0.35), any other gait related parameters, or in non-physical outcomes such as depression and fatigue. Conclusion: Inpatient group therapy task training for patients with moderate to severe stroke is safe and equally effective as a dose-matched individual task training therapy. Group therapy task training may be delivered as an alternative to individual therapy or as valuable adjunct to increase time spent in gait-related activities.