Ischemic Leukoencephalopathy Research Articles

Ultra-High Contrast MRI: Using Divided Subtracted Inversion Recovery (dSIR) and Divided Echo Subtraction (dES) Sequences to Study the Brain and Musculoskeletal System.

Divided and subtracted MRI is a novel imaging processing technique, where the difference of two images is divided by their sum. When the sequence parameters are chosen properly, this results in images with a high T1 or T2 weighting over a small range of tissues with specific T1 and T2 values. In the T1 domain, we describe the implementation of the divided Subtracted Inversion Recovery Sequence (dSIR), which is used to image very small changes in T1 from normal in white matter. dSIR has shown widespread changes in otherwise normal-appearing white matter in patients suffering from mild traumatic brain injury (mTBI), substance abuse, and ischemic leukoencephalopathy. It can also be targeted to measure small changes in T1 from normal in other tissues. In the T2 domain, we describe the divided echo subtraction (dES) sequence that is used to image musculoskeletal tissues with a very short T2*. These tissues include fascia, tendons, and aponeuroses. In this manuscript, we explain how this contrast is generated, review how these techniques are used in our research, and discuss the current challenges and limitations of this technique.

The bed smells like oil: About a case with diagnosis of epilepsy

IntroductionOlfactory hallucinations have been described since the 19th century as a particular, often unpleasant smell at the beginning or during the spell. The olfactory cortex are involved in temporal lobe epilepsy.ObjectivesThe aim was analyze the relationship between the olfactory hallucinations and the previus diagnosis of epilepsy.MethodsIn this study, we present a clinical case and review the current literature showing the relationship between smell and epilepsy.ResultsA 69-years-old woman, with a medical history of epilepsy, went to the emergency department describing a recent episode of seizure, self-limited in time, after a sensation of an unpleasant smell in bed. A medical history of osteoarthritis, cholecystectomy and essential tremor is described. No unknown drug allergies. The neurological examination shows dysarthric speech, tremor in the right upper limb, isochoric and reactive pupils, preserved sensitivity and strength, and a positive Romber’s sign. The physical examination, blood test and vital signs were normal. The head CT scan showed signs of ischemic leukoencephalopathy, without acute ischemic or hemorrhagic lesions. The patient was medicated with 1000 mg of valproate daily, which was suspended a month ago due to an alteration in liver transaminases. Treatment with diazepam 10 mg daily was prescribed and referred for consultation. The sense of smell changes over time for anormal aging process, affecting abilitiesto detect, identify and discriminate odors.Several neurodegenerative diseases presentcertain alterations that help us determine yourorigin and progression (Vaughan and Jackson, 2014).ConclusionsOlfactory auras occurs before a seizure of the temporal lobe. Repeated stimuli in limbic regions can produce changes in the piriform cortex, with increased excitability and in epileptic discharges.DisclosureNo significant relationships.

The use of methylphenidate in vascular dementia: A case report

IntroductionPatients diagnosed with vascular dementia often present with apathy, executive dysfunction or/and memory impairment. Some of these psychiatric domains are not responsive to antidepressants or acetylcholinesterase inhibitors. Since methylphenidate enhances frontal lobe function, it may be a valid therapeutic option.ObjectivesTo report a case where methylphenidate was used as a therapeutic approach in vascular dementia.MethodsWe present a case of a patient diagnosed with vascular dementia with substantial clinical improvement after treatment with methylphenidate.ResultsA 67 year-old male was observed in a psychiatric consultation reporting memory loss, inability to retain information and inattention. According to her spouse, the patient has been mostly isolated at home and recently he has become unable to accomplish some daily living activities. There was no history of previous psychiatric disorder. Cognitive assessment was performed using MoCA test: 19/30 points (predominantly in executive, attention and delayed recall domains). After this evaluation, it was introduced bupropion 150mg od and donepezil 5mg od with insignificant clinical improvement. The patient underwent a routine workup which was unremarkable and a brain computed tomography scan that revealed ischemic leukoencephalopathy. Three months later no clinical benefit was reported. Attention and functional improvement were observed after introduction of methylphenidate with progressive dose adjusting till 30 mg/day.ConclusionsBesides not being a consensual therapeutic approach, considering that there is a lack of efficient pharmacological strategies in vascular dementia, methylphenidate may play a significant role in this field contributing to clinical improving and ultimately to an enhanced quality of life.

Left ventricular ejection fraction and right atrial diameter are associated with deep regional CBF in arteriosclerotic cerebral small vessel disease

BackgroundSystemic cardiac hypoperfusion is a well-acknowledged contributor to ischemic leukoencephalopathy. However, it has remained elusive how atherosclerosis-mediated cardiac remodelling modifies cerebral perfusion homeostasis as well as neuroimaging burden in cerebral small vessel disease (CSVD) development.MethodsThis retrospective study identified 103 arteriosclerotic CSVD (aCSVD) patients (CSVD burdenlow 0 ~ 1, n = 61 and CSVD burdenhigh 2 ~ 4, n = 42) from Sep. 2017 to Dec. 2019 who underwent transthoracic echocardiography(n = 81), structural magnetic resonance imaging and arterial spin labelling (ASL). Total CSVD burden was graded according to the ordinal “small vessel disease” rating score (0–4). We investigated the univariate and multivariate linear regression of mean deep regional cerebral blood flow (CBF) as well as logistic regression analysis of CSVD burdenhigh.ResultsRight atrial diameter (B coefficient, − 0.289; 95% CI, − 0.578 to − 0.001; P = 0.049) and left ventricular ejection fraction (B coefficient, 32.555; 95% CI, 7.399 to 57.711; P = 0.012) were independently associated with deep regional CBF in aCSVD patients. Binary logistic regression analysis demonstrated decreased deep regional CBF (OR 0.894; 95% CI 0.811–0.985; P = 0.024) was independently associated with higher CSVD burden after adjusted for clinical confounders. Multivariate receiver operating characteristics curve integrating clinical risk factors, mean deep CBF and echocardiographic parameters showed predictive significance for CSVD burdenhigh diagnosis (area under curve = 84.25, 95% CI 74.86–93.65%, P < 0.0001).ConclusionThe interrelationship of “cardiac -deep regional CBF-neuroimaging burden” reinforces the importance and prognostic significance of echocardiographic and cerebral hemodynamic assessment in CSVD early-warning.

Bi-caudate ratio as a MRI marker of white matter atrophy in multiple sclerosis and ischemic leukocencephalopathy

BackgroundBrain atrophy measurement is now a cornerstone in basic neuro-imaging science. While assessment of white matter atrophy by visual inspection is subjective, volumetric approaches are time-consuming and not often feasible. Bi-caudate ratio represents a linear surrogate parameter of brain volume that can be derived from standard imaging sequences. This study highlights the value of the bi-caudate ratio (BCR) as a MRI marker of white matter atrophy in patients with multiple sclerosis and ischemic leukoencephalopathy and set a cut-off value to differentiate between patients with white matter atrophy and normal subjects.ResultsA total of 115 patients (54 males and 61 females) diagnosed with white matter leukoencephalopathy (MS in 51 patients and ischemic leukoencephalopathy in 64 patients) were included. Another group of 60 subjects with a normal white matter signal was recruited as a control group. BCR for the patient group ranged from 0.13 to 0.27 (mean (± SD) = 0.16 ± 0.02), while for the control group, it ranged from 0.05 mm to 0.13 (mean (± SD) = 0.09 ± 0.01). The difference between the two groups was statistically significant (P value < 0.001). A cut-off value of 0.13 was used to differentiate between the BCR in both patients and control groups with sensitivity, specificity, and accuracy of 99.2%, 100%, and 99%, respectively. The difference in BCR for patients diagnosed with MS and ischemic leukoencephalopathy was also statistically significant (P value < 0.001).ConclusionThe bi-caudate ratio represents a linear measurement of subcortical atrophy that can be useful as a surrogate marker of global supra-tentorial white matter atrophy instead of the usually performed visual and therefore subjective assessment. It is an easily obtained measure that can be performed without complex time-consuming volumetric studies. Our findings also revealed that the BCR is higher in patients with ischemic leukoencephalopathy than in patients with MS.

Acute hypoxic-ischemia in cardiac arrest encephalopathy causes only minimal demyelination.

The underlying pathological process of "ischemic leukoencephalopathy" is not well studied in humans and "demyelination" is thought to represent a major component. We selected brains from autopsy cases with definite histories of recent cardiac arrest, in which the autopsy findings demonstrated gray matter ischemic changes consistent with the survival time. We excluded cases with clinical or pathological evidence of other diseases that may affect the white matter, specifically those with moderate-severe edema. The selected cases were then subjected to a review of the gross pathology (photographs) and microscopy. We used the normal white matter areas in the same brains as internal controls to exclude artefactual changes. Sixteen cases were selected. The pathological changes in acute ischemic leukoencephalopathy include: white matter pallor with separation of myelinated fibers and fine vacuoles, coarse vacuoles with or without attenuated axons, apoptotic nuclei, axonal abnormalities, focal scattered demyelinated axons and infarcts. The interpretation of these findings is controversial (i.e. ischemia, edema, artifact or combination) due to the postmortem nature of the specimens. However, these factors should not affect our interpretation of minimal demyelination in the pathological process. The major underlying pathological process in acute ischemic leukoencephalopathy is axonal degeneration, while demyelination represents only a minor component.

A case of dementia secondary to subacute leukoencephalopathy by carbon monoxide

Introduction: Delayed hypoxic–ischemic leukoencephalopathy /INS;described in 1976 by Ginsberg is a brain white /INS;matter demyelinization phenomenon that occurred days or weeks after a hypoxic–ischemic /INS;injury followed by a complete recovery of the episode. Recovery is frequently observed in 75% of cases. We present the case of a patient exposed to carbon monoxide acutely, without impairment of consciousness that develops a subacute dementia syndrome.

Acute hydrocephalus following heroin induced leukoencephalopathy

Heroin-induced leukoencephalopathy is a rare complication of heroin intoxication, and always presents as hypoxic ischemic leukoencephalopathy with periventricular white matter edema and spongiform leukoencephalopathy in cerebral and cerebellar white matter [1, 2]. Acute hydrocephalus following toxic leukoencephalopathy has been reported in carbon monoxide and methadone intoxication [3, 4]. However, acute hydrocephalus following heroininduced leukoencephalopathy has not been previously reported. On 14 April 2011, a 37-year-old man found in a hotel presented to our hospital after 1 day of unconsciousness. The rubbish can in the man’s hotel room contained an empty syringe, and there were several needle holes in his forearm. Physical examination showed neck rigidity. Glasgow score on admission was 7/15 (E = 1/4, V = 3/5, M = 3/6). His personal and family history was negative for diabetes, seizure disorders, alcohol abuse, and vascular risk factors. There was no evidence of carbon monoxide poisoning. Hematological and biochemical examinations including hepatitis B, C virus and HIV serology were normal except for high levels of blood creatine kinase (847.24 U/L) and myoglobin (193 lg/L). Drug screening in urine showed positive for heroin. Lumbar puncture showed mildly increased intracranial pressure of 200 mmH2O, and cerebrospinal fluid routine test and biochemistry were negative. A magnetic resonance imaging (MRI) of the brain revealed abnormally low signal intensity in T1-weighted and high signal intensity in T2-weighted images in bilateral cerebellar hemispheres (Fig. 1a). No abnormality was found in the cerebral magnetic resonance angiography. Toxic leukoencephalopathy was suspected. Mannitol and dexamethasone were administered, and the man became confused on the second day. Surprisingly, a repeat MRI of the brain on the fifth day revealed enlarged lesions in the bilateral cerebellar hemispheres and compression in the fourth ventricle (Fig. 1b), and diffusion weighted image (DWI) showed a high signal intensity in the bilateral cerebellar hemispheres (Fig. 1c). The man fell into a coma accompanied by dyspnea on the seventh day of admission. A computed tomography (CT) of the brain showed hypodense lesions in bilateral cerebellar hemispheres, the fourth ventricle vanishing, and dilatation of the lateral and third ventricles, indicating acute obstructive hydrocephalus (Fig. 1d). Tracheotomy and surgical external drainage of the hydrocephalus were applied, the consciousness and respiration recovered on the twentieth day while the ataxia and pyramidal signs remained. A brain CT showed that the hydrocephalus was improved (Fig. 1e). The man admitted to 1 year of heroin abuse by intranasal and intravenous administration about 1–3 g a day and confirmed that he had injected an extensive quantity of heroin on the day of onset. This pattern confirmed the diagnosis of acute heroin intoxication accompanied with leukoencephalopathy and acute hydrocephalus. Following a month of treatment, his symptoms were resolved and the imaged lesions were absorbed (Fig. 1f). To the best of our knowledge, this report is the first description of acute hydrocephalus in heroin-induced H. Long J. Zhou X. Zhou Y. Xie B. Xiao (&) Neurology Department, Xiangya Hospital Central-south University, Changsha 410008, China e-mail: csulhy@yahoo.cn

Cerebral Small Vessel Disease in Pseudoxanthoma Elasticum: Three Cases

Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones. Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI. We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.

The neuropathology of vascular dementia

Ischemic infarction is the main lesion underlying vascular dementia (VaD) but cases also occur after brain hemorrhage, as well as with hypoperfusive brain ischemia. Ischemic strokes include large-vessel cortico-subcortical strokes and lacunes resulting from small-vessel disease. Arteriolosclerosis and fibrinoid necrosis are the most common forms of small-vessel disease in the elderly. Although it was originally proposed that vascular dementia could result from repeated strokes with loss of >100 mL of brain tissue loss (multi-infarct dementia), it is currently held that the location of the stroke is probably more relevant to cognitive loss and dementia. In fact, a single, strategically located stroke may interrupt cortico-subcortical circuits important for memory and cognition. Hypoperfusive lesions include border-zone cortico-subcortical infarcts, temporal lobe sclerosis, and periventricular incomplete ischemic leukoencephalopathy. The latter two lesions are commonly seen in the elderly as a result of narrowing and tortuosity of medullary arterioles irrigating these distal territories, plus cardiac pump failure. Binswanger disease is characterized by extensive periventricular ischemic leukoencephalopathy that spares the arcuate U-fibers, and presence of lacunar strokes. CADASIL is a genetic form of vascular dementia characterized by a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CADASIL is due to a mutation of the Notch3 gene in chromosome 19. Intracerebral hemorrhages in strategic locations may produce vascular dementia. Lesions in the basal forebrain that damage cholinergic nuclei, such as those resulting from a ruptured aneurysm of the anterior communicating artery, may produce vascular dementia. Some patients with subarachnoid hemorrhage develop normal-pressure hydrocephalus. Cerebral amyloid angiopathy (congophilic angiopathy) may cause lobar hemorrhages and dementia. Vascular lesions, in particular, microinfarcts, are frequently found in patients with a clinical diagnosis of Alzheimer disease. These mixed forms of dementia are likely to become the most common form of dementia in the elderly.

Cerebral Blood Flow and Oxygen Metabolism in Leuko-Araiosis

Regional blood flow and oxygen metabolism were determined by positron emission tomography using the steady-state technique with O-15, in 2 patients with posthypoxic ischemic leukoencephalopathy, in 6 patients with leuko-araiosis and dementia, and in 6 patients with leuko-araiosis without dementia. Comparison between the three groups allowed us to conclude that leuko-araiosis is associated with a lowered cerebral blood flow, which is more pronounced and widespread in demented patients and more restricted to the white matter in nondemented ones.

The identity of lacunar dementia and Binswanger disease

It is postulated here that the dementia occurring in patients with lacunar strokes is due to an ischemic leukoencephalopathy. Severity of the dementia correlates, not with the volume of brain tissue lost from large-artery infarctions, but rather, with the extent of cortex disconnection resulting from demyelination. The term Lacunar Dementia is proposed, instead of the poorly known eponym “Binswanger disease” or the cumbersome descriptive name “subcortical arteriosclerotic encephalopathy”. Clinically, Lacunar Dementia presents with gait difficulties, urinary incontinence, parkinsonian features, pseudobulbar palsy, emotional incontinence and dementia. High-resolution CT scan shows decrease density of frontal and periventricular white matter, without contrast enhancement; ventricular dilatation, and lacunar infarcts. Small-artery disease lipohyalinosis is the cause of the lacunes and the leukoencephalopathy. Since the advent of the high-resolution CT scan, the frequency of lacunar dementia seems to be increasing, in contrast with the number of cases of multi-infarct dementia.