Jan Malm

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.

Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study.

The prevailing view on multiple sclerosis etiopathogenesis has been challenged by the suggested new entity chronic cerebrospinal venous insufficiency. To test this hypothesis, we studied 21 relapsing‐remitting multiple sclerosis cases and 20 healthy controls with phase‐contrast magnetic resonance imaging. In addition, in multiple sclerosis cases we performed contrast‐enhanced magnetic resonance angiography. We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis. ANN NEUROL 2010;68:255–259

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.

Regional cerebral blood flow, white matter abnormalities, and cerebrospinal fluid hydrodynamics in patients with idiopathic adult hydrocephalus syndrome.

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.

Influence of comorbidities in idiopathic normal pressure hydrocephalus — research and clinical care. A report of the ISHCSF task force on comorbidities in INPH

Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes.

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.

CSF hydrodynamics in idiopathic intracranial hypertension A long‐term study

To examine CSF hydrodynamics, we studied 16 patients with idiopathic intracranial hypertension and 45 control subjects with a constant-pressure infusion method. Fifteen patients had 155 examinations up to 15 years after the onset of disease. In most patients, the disturbances of CSF hydrodynamics persisted for many years. We identified at least two mechanisms for the development of the increased CSF pressure: a rise of sagittal sinus pressure, probably explained by extracellular edema causing partial compression of the major venous sinus (type 1), or a low conductance with a compensatory increase in CSF pressure in order to sustain the bulk flow (type 2).

Assessment of cerebrospinal fluid outflow resistance

The brain and the spinal cord are contained in a cavity and are surrounded by cerebrospinal fluid (CSF), which provides physical support for the brain and a cushion against external pressure. Hydrocephalus is a disease, associated with disturbances in the CSF dynamics, which can be surgically treated by inserting a shunt or third ventriculostomy. This review describes the physiological background, modeling and mathematics, and the investigational methods for determining the CSF dynamic properties, with specific focus on the CSF outflow resistance, Rout. A model of the cerebrospinal fluid dynamic system, with a pressure-independent Rout, a pressure-dependent compliance and a constant formation rate of CSF is widely accepted. Using mathematical expressions calculated from the model, along with active infusion of artificial CSF and observation of corresponding change in ICP allows measurements of CSF dynamics. Distinction between normal pressure hydrocephalus and differential diagnoses, prediction of clinical response to shunting and the possibility of assessment of shunt function in vivo are the three most important applications of infusion studies in clinical practice.

CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus

Background –  To evaluate cerebrospinal fluid (CSF) markers for neuronal degeneration and demyelination in idiopathic normal pressure hydrocephalus (INPH), subcortical arteriosclerotic encephalopathy (SAE), and neurologically healthy subjects.

Idiopathic normal pressure hydrocephalus

Hydrocephalus can present with acute or chronic symptoms at any age. Obstructive and communicating hydrocephalus are the two main types. In adults, the most common form of the latter is normal pressure hydrocephalus (NPH) with a mean age at onset of about 70 years, equally common in both sexes. This review will focus on the idiopathic variant of the disease (INPH), the typical features of which are imbalance, gait disturbance, urinary symptoms, and cognitive decline. Although the treatment is surgical, by placing a cerebrospinal fluid (CSF) shunt, neurologists are essential for diagnosing patients with gait disturbance and/or ventriculomegaly, for preoperative selection of shunt candidates, and to optimise the CSF shunt system postoperatively. Very little is known about the incidence and prevalence of INPH. In a door to door survey in people older than 65 years, 0.7% of the population had Parkinson’s disease and 0.4% NPH.1 In Sweden, between three and six shunt operations in adults per 100 000 inhabitants are done every year at the six neurosurgical centres, about 30% of which are for INPH and 20% for secondary NPH.2 The pre- and postoperative investigation of INPH is the fourth most common diagnosis after stroke, epilepsy, and headache at the neurology inpatient service at our hospital. There are few neurological conditions where treatment has such a large impact on outcome as INPH. The patients are elderly and even a small improvement in their gait or activities of daily living has the potential to substantially increase their independence. In most countries hydrocephalus is considered a “neurosurgical problem” without any need to consult the neurologist. But we believe that a multidisciplinary approach with the neurologist and neurosurgeon in fruitful cooperation is what is needed. An important issue for the general neurologist is the evaluation of patients referred because of gait …