P75 nerve growth factor receptor is expressed in regenerating human nerve grafts.

BACKGROUND: The purpose of this study was to elucidate the expression of p75 nerve growth factor receptor (p75NGFR) in human cross-facial nerve grafts and to compare the immunohistological findings with patient data and the functional outcome in facial reanimation. MATERIALS AND METHODS: The study comprised 37 sural nerve graft specimens. All of the patients had long-lasting complete facial paralysis and were operated on by the standard two-stage procedure involving cross-facial nerve grafts and microneurovascular muscle transfer. Nerve biopsies were taken 4 to 20 months (mean, 8 months) after the cross-facial nerve grafting. Immunohistochemistry for p75NGFR as well as for Schwann cells (S-100; Dako, Glostrup, Denmark) and for Neurofilament-200 (NF-200; Boehringer, Mannheim, Germany) was performed. RESULTS: In graft biopsies, the mean number of NF-200-positive axons amounted to 38% (range, 6-81%) of that in control samples. Further, regenerated axons were thinner than in control samples. Morphologically, the grafted nerves were characterized by fibrosis and invasion of inflammatory cells. A longer time between cross-facial nerve grafting and biopsy sampling correlated with a higher number of viable axons (NF-200) (P = 0.002). In all cases, expression of p75NGF receptor was clearly higher at the distal end of the grafted nerve. Expression of p75NGFR was lower in older than in younger patients (P = 0.003). A high expression of p75NGFR was often seen with better function of the transplanted muscle. CONCLUSION: Increased expression of p75NGFR in human nerve grafts was noted, especially in younger patients. We suggest that p75NGFR expression might be a contributing factor in a successful axonal regeneration and eventual recovery of muscle function.

Magnetic resonance imaging of microneurovascular free muscle flaps in facial reanimation.

The purpose of this study was to describe the survival and volume of microneurovascular muscle flaps at different times after two-stage facial reanimation procedure by using magnetic resonance imaging (MRI) and to compare the functional outcome with MRI findings. Fifteen patients with a mean age of 36 years (range 7-63 years) operated on between 1988 and 1999 were available for this study. The muscles used for functional reconstruction were the latissimus dorsi (eight patients), gracilis (six patients) and serratus anterior (one patient). Hospital charts were reviewed and the clinical outcome of facial reanimation was graded on a scale from 1 to 6 according to House. The mean postoperative follow-up time was 7 years (range 3-14 years). Clinical grading and 1.5 T unit MRI of patients were performed concomitantly. The MR images were evaluated semi-quantitatively so that the muscle structure of the free flaps was graded on a scale from 1 to 4. The free flap area of each slice was defined and the volume of the free flap was calculated. Data were analysed statistically. The long-term functional outcome of the facial reanimation was regarded as good in 10 patients, which means they had only mild or moderate dysfunction of facial movements. In MR images, six free flaps displayed normal muscle structure, another six had a fatty appearance and two displayed severe muscle atrophy; in one patient the muscle tissue could not be identified. The volume of the free flap clearly declined in the course of the follow-up. A correlation was found between good functional outcome and normal muscle structure of the free flap in MRI, p = 0.020. The longer the follow-up time after muscle transplantation the poorer the functional result. A similar correlation was found between abnormal muscle structure in MRI and a long follow-up time. Magnetic resonance imaging can be used to assess the muscle structure of free microneurovascular flaps. Normal findings in MRI seem to correlate with a good clinical outcome in facial reanimation. A good functional result correlates with a shorter follow-up time and normal muscle structure in MRI.

Facial reanimation by transplantation of a microneurovascular muscle: long-term follow-up.

The two-stage operation for reanimation of long-standing facial paralysis by cross-facial nerve grafting and later free microneurovascular muscle transfer has been the treatment of choice for nearly 25 years. However, the functional outcome may be unpredictable. We therefore need to know more about the factors that influence the final result. We have recorded the long-term results of microneurovascular surgery in facial paralysis, and evaluated which factors influenced the functional outcome. Twenty-seven of 40 patients aged 7 to 65 years (mean 40) operated on at Helsinki University Hospital between 1986 and 2000 were available for interview and video recording. The gracilis, latissimus dorsi, and serratus anterior muscles were used for microneurovascular transfer in 11, 10, and 6 cases, respectively. The outcome of microneurovascular muscle transfer was graded on House's scale 1 to 6. The mean follow-up period was 8.5 years (range 2 to 15). Sixteen patients (59%) displayed only mild or moderate dysfunction (grades 2 to 3) after reconstruction. In 8 patients (30%) dysfunction was graded as moderately severe, and in 3 (11%) as severe. There was a correlation between final functional outcome and the follow-up time after microneurovascular facial reanimation. The longer the follow-up time after muscle transplantation the poorer the functional result (p = 0.003). Twenty-one patients (78%) considered that their quality of life was better or much better after facial reanimation. Patients' satisfaction correlated with a good functional result.

Long-term morphometric and immunohistochemical findings in human free microvascular muscle flaps.

Reinnervation, muscle regeneration, density of microvessels, and muscle-type specific atrophy were studied 3-4 years after surgery in surgically nonreinnervated free microvascular muscle flaps to 13 patients transplanted to the upper or lower extremities. Routine histology and immunohistochemistry for PGP 9.5 and S-100 (neuronal markers), Ki-67 (cell proliferation), myosin (muscle fiber types), and CD-31 (endothelium) were carried out, and results were analyzed morphometrically. Three to 4 years after surgery, severe atrophy of predominantly slow-type fibers was seen in 9 cases. In 4 cases, muscle-fiber diameter and fiber-type distribution were close to normal. Long intraoperative muscle ischemia and postoperative immobilization were associated with poor muscle bulk in flaps. The density of microvessels in flaps did not differ from control muscles. PGP 9.5 and S-100 immunopositive nerve fibers were detected in 7 patients. Reinnervation was associated with good muscle bulk. In 4 patients, activation of satellite cells was evident. The results suggest that in some cases, spontaneous reinnervation may occur in free muscle flaps, and that several years after microvascular free flap transfer, the muscle still attempts to regenerate.

Domains and determinants of quality of life after stroke caused by brain infarction.

OBJECTIVE: To evaluate the domain-specific quality of life (QOL), including physical, social and role functioning, mental health, vitality, bodily pain, and general health domains, and to assess QOL's clinical and sociodemographic correlates in patients who were disabled by ischemic stroke. DESIGN: One-year prospective study of an inception cohort of patients with first-ever brain infarction. SETTING: Stroke unit of a neurologic department of a university hospital. PATIENTS: Eighty-five consecutive patients (36 women, 49 men; mean age +/- SD, 65+/-12.5 yr) with first-ever stroke of a mild to moderate nature caused by brain infarction. MAIN OUTCOME MEASURES: Patients were examined at 3 and 12 months poststroke. QOL was measured using the RAND 36-Item Health Survey. The variables studied were lateralization of cerebral lesion, neurologic and functional status, depression, age, gender, marital status, and living conditions. Depression was evaluated according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Neurologic impairment was assessed by Scandinavian Stroke Scale, performance in activities of daily living by the Barthel index, and the intellectual deterioration by the Mini-Mental State Examination. RESULTS: QOL was poorer for the patients with mild to moderate stroke impairments at 3 months poststroke. The test domains most prone to being affected were physical functioning, physical role limitations, vitality, and general health. Only the domains of physical functioning and physical role limitations improved during the follow-up at 1 year. Depression, although mostly minor, was the most important reason for impaired QOL. Depression, being married, and age emerged as significant independent contributors to the low score value of vitality. Depression and being married were related to the low score value of physical role limitations. CONCLUSIONS: Stroke affects QOL, impairing its physical and psychosocial domains. The most important determinants of low QOL seem to be depression and being married. These findings provide new challenges for stroke rehabilitation, calling for identification of patients and spouses in need of supportive services.

Aphasia, depression, and non-verbal cognitive impairment in ischaemic stroke.

Aphasia, depression, and cognitive dysfunction are common consequences of stroke, but knowledge of their interrelationship is limited. This 1-year prospective study was designed to evaluate prevalence and course of post-stroke aphasia and to study its psychiatric, neurological, and cognitive correlates. We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65. 8 years) with first-ever ischaemic brain infarction. The patients were clinically examined, and presence and type of aphasia were evaluated during the 1st week after stroke and 3 and 12 months later. Psychiatric and neuropsychological evaluations were performed 3 and 12 months after stroke. Aphasia was diagnosed in 34% of the patients during the acute phase, and two thirds of them remained so 12 months later. Seventy percent of the aphasic patients fulfilled the DSM-III-R criteria of depression 3 months and 62% 12 months after stroke. The prevalence of major depression increased from 11 to 33% during the 12-month follow-up period. The non-verbal neuropsychological test performance in the aphasic patients was significantly inferior to that of the patients with dominant hemisphere lesion without aphasia. One third of the patients with ischaemic stroke suffer from communicative disorders which seem to increase the risk of depression and non-verbal cognitive deficits. Although the prevalence of depression in aphasic patients decreases in the long term, the proportion of patients suffering from major depression seems to increase. We emphasize the importance of the multidimensional evaluation of aphasic stroke patients.

Auditory P300 event related potential in minor ischemic stroke.

OBJECTIVE: Various degenerative cerebral diseases and even depression may cause abnormalities of the cognitive event related potentials (ERPs). We conducted the present study to elucidate the effects of ischemic stroke on the P300 ERP component. MATERIAL AND METHODS: We recorded the P300 wave using an auditory oddball paradigm in 38 consecutive brain infarct patients with mild neurological deficits at 3 and 12 months post-stroke, and in 29 healthy control subjects. RESULTS: Brain infarction slightly prolonged the P300 latency, and the observed delay was related to the presence and degree of post-stroke depression evaluated with the Zung Depression Scale and the DSM-III criteria. Infarction did not affect the P300 amplitude or its distribution on the scalp. The results of the patients with hemispheric brain infarction and those of the patients with brainstem infarction were similar, and also the values of the patients with the left- and right-sided lesions. The normal physiological correlation between subject age and the P300 latency was absent at 3 months post-stroke, but was present at 12 months post-stroke. CONCLUSION: Brain infarction delays the P300 ERP and temporarily distorts its age-related physiology. The increase of the P300 latency seems to be associated with the post-stroke depression.

Poststroke depression correlates with cognitive impairment and neurological deficits.

BACKGROUND AND PURPOSE: The prevalence of poststroke depression is known to be high, but the knowledge of its neuropsychological correlates is limited. This 12-month prospective study was designed to evaluate the natural history of poststroke depression and to study its neuropsychological, clinical, and functional associates. METHODS: We studied a series of 106 consecutive patients (46 women and 60 men, mean age 65.8 years) with acute first-ever ischemic stroke. The patients underwent a neurological, psychiatric, and neuropsychological examination at 3 and 12 months after the stroke. The psychiatric diagnosis of depression was based on DSM-III-R-criteria. RESULTS: Depression was diagnosed in 53% of the patients at 3 months and in 42% of the patients at 12 months after the stroke. The prevalence of major depression was 9% at 3 months and 16% at 12 months. There was an association between poststroke depression and cognitive impairment; the domains most likely to be defective in stroke-related depression were memory (P=0.022), nonverbal problem solving (P=0.039), and attention and psychomotor speed (P=0.020). The presence of dysphasia increased the risk of major depression. The depressive patients were more dependent in ADL and had more severe impairment and handicap than the nondepressive patients. CONCLUSIONS: More than half of the patients suffer from depression after stroke, and the frequency of major depression seems to increase during the first year. In addition to dysphasia, poststroke depression is correlated with other cognitive deficits. We emphasize the importance of psychiatric evaluation of stroke patients.

Muscle fiber diameter and muscle type distribution following free microvascular muscle transfers: a prospective study.

The histology of free microvascular muscle flaps in 19 patients was studied prospectively. Biopsies were taken during operation, and after 2 and 6 weeks, as well as 3, 6, and 9 months, postoperatively, fixed and stained using the van Gieson method. Fiber diameters were analyzed morphometrically and fiber types defined immunohistochemically using myosin fast antibody. During the nine-month follow-up period, mean muscle fiber diameter decreased significantly (P < 0.01), type-1 fibers atrophied significantly (P < 0.05) compared to type-2 fibers, and the percentage of type-2 fibers increased from a mean of 56% intraoperatively to 73% at 9 months. Fatty change and fibrosis were already present 2 weeks after operation and increased with the duration of follow-up. The decrease in muscle fiber diameter 9 months after free flap transfer correlated with clinical factors such as the delay of reconstructive surgery, recipient site, postoperative infection, and postoperative immobilization. The present results confirm that type-specific atrophy related to denervation appears and indicates that clinical events other than denervation influence the muscle atrophy seen in human free muscle flaps. These findings focus attention on the role of muscle regeneration, reinnervation, and revascularization taking place after free flap transfer.

Sexual dysfunction in stroke patients.

OBJECTIVES: A marked decline in sexual activity has been reported in stroke patients. Little information, however, is available on clinical correlates of sexual dysfunction, changes in the sexual life of spouses of stroke patients, and abnormalities of nocturnal penile erections. MATERIAL AND METHODS: In this prospective 6-month follow-up study, we assessed the impact of stroke on libido, sexual arousal, coital frequency and satisfaction with sexual life in 50 stroke patients (38 men, 12 women, aged 32 to 65 years) and in their spouses. We also measured nocturnal penile erections of the male patients using a strain gauge attached around the penis. RESULTS: All the analyzed aspects of sexuality, i.e., libido, coital frequency, erection, ejaculation, vaginal lubrication, orgasm and satisfaction with sexual life, were commonly decreased as a consequence of stroke both in the patients and in their spouses. Fourteen (28%) patients at 2 months post-stroke and 6 (14%) patients at 6 months had ceased having sexual intercourse. Nocturnal erections at 2 months post-stroke were normal in 17 (45%) of the 38 male patients and impaired in 21 (55%) patients, but all of the patients had some nocturnal erections. Sexual dysfunction correlated significantly (P<0.05) with the presence of the sensory hemisyndrome. CONCLUSIONS: Sexual dysfunction and dissatisfaction with sexual life seems to be common both in male and female stroke patients and in their spouses. Decreased libido, sexual arousal and satisfaction are related particularly to the presence of the hemisensory syndrome. The etiology for sexual dysfunction after stroke is multifactorial including both organic and psychosocial factors.