Markku Fagerlund

Epidemiology and Etiology of Ischemic Stroke in Young Adults Aged 18 to 44 Years in Northern Sweden

BACKGROUND AND PURPOSE The aim of this study was to conduct a population-based epidemiological survey among young adults aged 18 to 44 years in Northern Sweden and furthermore to gain further insight into the etiology of ischemic stroke in this age group. METHODS Two studies were done. In the first part, epidemiological data were collected to calculate incidence and mortality from 1991 through 1994. This was based on the World Health Organization Northern Sweden MONICA register of acute stroke events. Eighty-eight first-ever ischemic stroke patients were identified during that period. In the second part, 107 consecutive patients aged 18 to 44 years with ischemic stroke referred to a university hospital were studied prospectively during a 5-year period and were extensively evaluated according to a standardized protocol. On the basis of modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, the patients were classified into eight subtypes of ischemic stroke. RESULTS The average population-based annual incidence rate for ischemic stroke (cases per 100,000 per year) was 11.3 (95% confidence interval, 6.7 to 16.1). The case-fatality rate was 5.7%. According to the modified TOAST criteria, a probable cause of ischemic stroke was identified in 36% and remained unexplained in 21% of cases. Spontaneous cervical arterial dissection was the leading probable etiology (13%). Patent foramen ovale or atrial septal aneurysm was a possible cause of stroke in 28% of cases. The percentages of ischemic stroke attributed to IgG anticardiolipin antibodies (4.7%), atherothrombotic vasculopathy (3.7%), oral contraceptive use (7%), and migraine (1%) were lower than reported in recent clinical series. CONCLUSIONS The incidence rate for ischemic stroke was higher than previously reported from most countries in Western Europe. The higher incidence was not explained by a higher prevalence of premature atherosclerotic vasculopathy. Without the additional diagnostic information derived from advanced cardiac imaging, the proportion of indeterminate cases would have constituted 37% of the patients.

An adapter for computed tomography-guided stereotaxis

A new, versatile adapter for computed tomography-guided stereotaxis is presented. The instrument consists of a light aluminum frame, which by means of a nasion support and two ear plugs is fixed to the patients head. Reproducibility of repeated fixations is very high. The adapter is fitted to most stereotactic frames and can be used in all adult patients. Comparison between computed tomography- and ventriculography-guided determinations of thalamic targets showed a mean difference of 0.6 and 0.7 mm for the x and y coordinates, respectively. The z coordinates seldom showed any measurable difference. We now perform all types of stereotactic neurosurgery (tumor biopsy, implantation of depth electrodes, thalamotomy, dentatotomy, cingulotomy, etc.) with computed tomography guidance only. The short-term results in a small number of patients have been at least as good as after conventional ventriculography-guided surgery. In addition to open stereotactic surgery, the adapter is also suitable for external stereotactic irradiation of intracranial targets with a linear accelerator.

Cognitive impairment in young adults with infratentorial infarcts

Objective: To describe cognitive functions and functional outcome in young patients with isolated infratentorial infarcts. Background: Contemporary knowledge implies a cerebellar contribution to cognitive behavior. Neuropsychological examination of patients with selective cerebellar lesions provides an opportunity to document the existence and nature of clinically relevant cognitive manifestations from lesions of the cerebellum. Methods: Prospective case series. The patients were assessed acutely and at 4 and 12 months after onset. Twenty-four patients from a consecutive series of 105 patients aged 18 to 44 years with cerebral infarction had a brain stem or cerebellar infarction. Fourteen age-matched controls were used for neuropsychological comparisons. Evaluation included MRI, angiography, and transesophageal echocardiography. Disability and neurologic dysfunction were assessed by the modified Rankin scale, NIH stroke scale, and maximal working capacity. A comprehensive neuropsychological battery was performed at baseline in 20 of the 24 patients. Results: Eighteen patients had a cerebellar infarct. Two patients had lateral medullary infarcts, and two isolated pontine infarcts. Twenty-two patients had a favorable outcome according to the modified Rankin scale (grade 0-2) and the NIH scale. In contrast, 12 patients were granted full or partial sick leave at the 4 months follow-up, and 10 patients at 12 months. Patients generally performed worse than controls in various aspects of cognitive function, especially in tasks concerning working memory, the temporary storage of complex information, and cognitive flexibility. Measures of verbal IQ (r = -0.74) and performance IQ (r = -0.78) were related to the size of the infarct. The block design task performance in the early poststroke period predicted maximal working capacity at 12 months. Conclusions: Cerebellar damage impairs central aspects of attention and visuospatial skills. In contrast, intelligence and episodic memory remain unchanged. When the lesion involves large portions of the cerebellar hemispheres, changes concerning broad areas of intelligence may occur. The prognosis is favorable for neurologic dysfunction, but cognitive deficits may prevent return to work.

Thigh musculature in relation to chronic anterior cruciate ligament tear: Muscle size, morphology, and mechanical output before reconstruction

Eighteen male patients who had untreated chronic ACL rupture were studied in order to evaluate thigh muscle size, morphology, and isokinetic performance of the quadriceps muscle. Computed tomography disclosed a 5.1 % mean atrophy of the quadriceps (P < 0.05), 2.1% slight hypertrophy of the hamstrings (P > 0.05), and also nonsignificant changes of all other muscle areas of the injured thigh. Muscle morphology (m. vastus lateralis) was normal in 11 biopsy specimens, whereas minor abnormalities (irregular shape or hypotrophy) could be seen in the rest. Isokinetic mechanical output of the knee extensors was 71% to 87% of that of the noninjured limb (P < 0.01), and the mechanical output corrected for differences in quadriceps cross-sectional area was significantly lower in the injured than the uninjured limb. As there were no significant correlations between isokinetic performance and muscle size or qualitative morphology or morphometric data, the strength decrease cannot be explained by muscle atro phy or structural changes per se. We conclude that nonoptimal activation of the muscles during voluntary contractions is probably the most important causative mechanism of the strength decrease found in patients who have chronic symptomatic ACL tear.

Disc pathology after whiplash injury. A prospective magnetic resonance imaging and clinical investigation.

STUDY DESIGN This study was used to evaluate the relationship between magnetic resonance imaging findings and clinical findings after whiplash injury. OBJECTIVES To identify initial soft-tissue damage after whiplash injury, the development of disc pathology, and the relationship of disc pathology to clinical findings. SUMMARY OF BACKGROUND DATA Although a few studies have reported pathological magnetic resonance imaging findings after whiplash injuries, there is no prospective study published to our knowledge. METHODS Thirty-nine patients, 20 women and 19 men with a mean age of 32 years, were treated for whiplash injury. Magnetic resonance imaging and clinical examination were performed in a blinded manner at a mean of 11 days after trauma. The procedure was repeated at a 2-year follow-up visit. Two patients could not be examined with the second magnetic resonance imaging because of claustrophobia and pregnancy, respectively. RESULTS The authors found 13 patients (33%) with disc herniations with medullary (six cases) or dura (seven cases) impingement over the 2-year follow-up period. At the follow-up examination all patients with medullary impingement had persistent or increased symptoms, and three of 27 patients (11%) with no or slight changes on magnetic resonance imaging had persistent symptoms. No ligament injuries were diagnosed. CONCLUSION Although disc pathology seems to be one contributing factor in the development of chronic symptoms after whiplash injury, it may be unnecessary to examine these patients in the acute phase with magnetic resonance imaging; correlating initial symptoms and signs to magnetic resonance imaging findings is difficult because of the relatively high proportion of false-positive results. Magnetic resonance imaging is indicated later in the course of treatment in patients with persistent arm pain, neurologic deficits or clinical signs of nerve root compression to diagnose disc herniations requiring surgery.

Cognitive Dysfunction, Hippocampal Atrophy and Glucocorticoid Feedback in Alzheimer’s Disease

BACKGROUND The hippocampal formation is damaged early in Alzheimers disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimers Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimers disease.

Three-year survival and functional outcome of patients with idiopathic adult hydrocephalus syndrome

Article abstract The functional outcome of 42 patients with idiopathic adult hydrocephalus syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves were compared with those of age-matched healthy elderly subjects and patients with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3 months after the operation and 11 remained improved at the 3-year follow-up. The case fatality in patients with stroke and those with IAHS was similar (32% versus 28%), but the relative risk of death among IAHS patients compared to a general elderly population was 3.3.

Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency: a case study.

We report a patient with advanced Parkinsons disease, including severe and frequent off periods with freezing of gait, moderate dysphonia, and some cognitive impairment, who underwent bilateral subthalamic nucleus (STN) stimulation. The patient was followed for 1 year after surgery, showing persistent good mobility without off periods and without freezing, which reverted completely when stopping the stimulation. There was deterioration of cognition as well as increased aphonia and drooling, all of which remained when the stimulation was turned off. The striking improvement in motor symptoms following STN stimulation was not paralleled by improvement in disability, probably as a result of a cognitive decline, suggesting a diagnosis of Parkinsons disease with dementia. We conclude that chronic STN stimulation is efficient in alleviating akinetic motor symptoms including gait freezing; this surgery should be offered before patients start to exhibit speech or cognitive disturbances.

MRI and neurology in acute whiplash trauma: No correlation in prospective examination of 39 cases

39 consecutive cases of whiplash injury of the neck were examined clinically and with MRI at a mean of 11 days after trauma. 26 of these showed changes on MRI with disc lesions in 25, 10 of which were classified as disc herniations, and a muscle lesion in 1 case. All had neck pain or headache. 29 cases had neurological deficits, mostly sensibility disturbances. 22 of the 26 cases with pathologic MRI findings had neurological signs, as had 7 of the 10 cases with disc herniation. The relationship between the MRI findings and the clinical symptoms and signs was poor.

Hypercortisolism after stroke--partly cytokine-mediated?

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is common early after stroke. Hypercortisolism is a prominent manifestation. Normally the secretion of cortisol is regulated by adrenocorticotrophic hormone (ACTH), but recently an ACTH/cortisol dissociation after stroke was reported. Cytokines may influence the HPA axis, and plasma IL-6 levels are elevated following stroke. We investigated correlations between cortisol, ACTH, and cytokines, and between blood pressure and blood hormone levels early after stroke in seven stroke patients. All had neurological symptoms secondary to brain infarctions. Blood samples for analysis of cortisol, ACTH, IL-6, TNF alpha, norepinephrine, and epinephrine were collected four times daily, and 24-h blood pressure was measured. Plasma IL-6, but not ACTH, correlated significantly to serum cortisol. Catecholamine levels correlated with cytokine and cortisol levels. This study suggests that several routes for HPA-axis dysregulation is present early after stroke. Cytokine release may play an important role in this situation.