Multifocal White Matter Research Articles

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) presents as an acute-onset neurological dysfunction following a triggering event such as an infection or vaccination. Patients present with polysymptomatic neurological dysfunction, and imaging shows multifocal white matter lesions in the brain and spinal cord. Clinical evaluation, magnetic resonance imaging, and cerebrospinal fluid study are most useful in establishing the diagnosis and ruling out important differential diagnoses. Corticosteroids are the mainstay of treatment and the role of other modalities of treatment, such as plasma exchange and intravenous immunoglobulin, require further study. Prognosis is generally good. The recently proposed consensus definitions are likely to facilitate delineation of ADEM from other acquired demyelinating disorders.

Severity of cerebral white matter lesions and infarcts in patients with transient or moderately disabling cerebral ischaemia: reproducibility of grading by neurologists

Diffuse or multifocal ischaemic white matter lesions increase the risk of intracranial haemorrhage in patients using oral anticoagulants for secondary prevention after cerebral ischaemia of arterial origin. We studied whether neurologists could reliably assess the presence of these white matter abnormalities. As part of the European/Australian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), the severity of white matter lesions and presence of ischaemic lesions were twice assessed in a consensus meeting of three neurologists (from a pool of nine) as absent, moderate or severe, in a sample of 126 randomly selected CT or MRI scans. The neurologists were not aware of the duplicate grading. The degree of agreement between the first and second observation was calculated with kappa statistics. The kappa value for agreement between the first and second assessment of white matter lesions was 0.58 (95% CI 0.40-0.76). The kappa value for the presence of clinically relevant and/or irrelevant ischaemic lesions was 0.68 (95% CI 0.58-0.78). Clinicians can assess the presence of white matter lesions with sufficient reliability. Such assessment may prevent unnecessary risk with oral anticoagulation in secondary prevention after cerebral ischaemia of arterial origin, of which the efficacy is currently being assessed in ESPRIT.

Inflammatory/demyelinating central nervous system involvement in familial Mediterranean fever (FMF): coincidence or association?

Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by recurrent febrile polyserositis. Central nervous system (CNS) involvement in FMF is uncommon, but recently cases with multiple sclerosis (MS) and FMF have been reported. Here we assess patients with both FMF and MS, in order to clarify any relationship between FMF and MS, and to evaluate disease characteristics. Our MS database between 1986-2005 was screened retrospectively, and patients with both FMF and inflammatory/demyelinating CNS disease were evaluated among a total of 2800 patients including definite MS (n = 2268) and other demyelinating disorders. There were 12 patients with FMF, who developed a CNS disorder with multifocal white matter lesions. Median age at onset of FMF was 7 years, and median age at neurological onset was 26.8 years. Nine patients (including two siblings) had definite MS according to clinical and MRI findings, whereas 3 patients had atypical features suggesting other demyelinating disorders. Disease severity varied among the patients between very mild to a fatal course. All 8 patients evaluated for oligoclonal IgG bands in CSF were positive. The rate of FMF among our patients with definite MS is almost 4 times the expected prevalence in Turkey. Our series including a sibling pair concordant for FMF and MS may suggest that similar genetic susceptibility and environmental factors might be responsible, although coincidence still remains a possibility. A prospective study on a larger sample seems to be justified.

Unusual magnetic resonance findings in two children with sudden sensorineural hearing loss

To describe the MRI findings of two pediatric patients with sudden sensorineural hearing loss (SSHL). Two male patients (two-year and three-months-old, and one year and four-months-old) presented with sudden dumbness. Physical and neurological examinations were unremarkable besides bilateral hypoacusia. All the laboratory investigation was negative, and brain stem auditory evoked potentials showed deep bilateral deafness in both cases. MRI studies revealed normal inner ears and multifocal white matter areas of slight low signal on T1-weighted images and high signal on FLAIR images. The follow-up MRI studies and neurological examinations did not demonstrate alterations in the previous findings. Pediatric patients with SSHL may present cerebral white matter signal abnormalities at the MRI as the only finding. Further studies with larger casuistics need to be conducted to elucidate these findings.

Invited Speaker for Scientific Session

Migraine is well accepted as a frequently disabling episodic malady, but the concept that the disorder may be associated with progressive and persistent symptoms or brain complications is fraught with controversy and a reluctance of many clinicians to acknowledge to their patients that such issues exist. Nevertheless, literature accrued in recent years speaks to the potential for long-term changes in the phenotypic expression of episodic migraine to a chronic form of headache. Often expressed subclinically, structural brain changes associated with migraine, although uncommon, may range from progressive cellular damage in nociceptive systems, diffuse white and grey matter loss, multifocal white matter lesions, and ischaemic stroke. Accordingly, this presentation will review and critique: • Clinical evidence for shift in phenotype • Neuropsychological testing • Epidemiological data • Cross-sectional prevalence studies • Longitudinal outcomes studies • Impact on comorbid conditions • Comorbid diseases • Mechanisms and markers of progression • Imaging • Markers of inflammation (CRP, metalloproteases) From this evidence, a small but potentially problematic group of migraine patients appear at risk for progression. Migraine may also impact the progression of comorbid diseases such as epilepsy. Duration, frequency and severity of migraine attacks are among risk factors for progression, but future studies need to further elucidate risk factors and markers to identify patients at risk of progression who may require aggressive management. Mechanisms underlying progressive disease are multifactorial but appear linked to the mechanisms and subtype of the attack itself.

Imaging in multiple sclerosis

Multiple sclerosis (MS) is a common central nervous system (CNS) disease characterised pathologically by the development of multifocal inflammatory demyelinating white matter lesions. Magnetic resonance imaging (MRI) is the gold...

A different look at biogeochemistry

<h3>Background</h3> The neurotrophic effects of Covid-19 are becoming increasingly recognized, with altered mental state now being the second most common presenting complaint insert numbers. A key question is whether this has long term consequences. Cognitive problems are commonly reported in patients 3 months after acute infection as part of the so called Long-Covid syndrome. However, the underlying cause is not well understood. Candidate explanations include legacy from encephalitis and stroke; however, other complications such as the sequelae, delirium, remain underexplored. Furthermore, little consideration has been given to functional cognitive disorders and the cognitive consequences of depression, anxiety and fatigue. <h3>Aims</h3> We propose a structured approach to clinical assessment for clinicians reviewing late cognitive complaints after COVID 19. <h3>Methods</h3> We created our own unique framework for neurocognitive Covid assessment based upon a review of the literature. <h3>Results</h3> Covid status- Any positive test. If not review of core symptoms such as breathlessness, headache, anosmia, nasal obstruction, cough, myalgia, or gustatory dysfunction; duration, extent of exposure to Covid confirmed cases. Consider rapid antibody testing. Neuropsychiatric history- Part 1 symptoms at onset- in particular disruptions of consciousness and altered mental state. Acute memory impairment, anterograde/retrograde and with/without a temporal gradient. neurocognitive function. ITU admission and oxygen requirements. Part 2 Current cognitive and mental state- in addition to standard history seek evidence of internal inconsistency of memory symptoms and attentional dysregulation. Has social cognition and meta-cognition been affected. Note attribution bias i.e. no Im not depressed, I cant enjoy anything because of my symptoms Background history- subtle suggestion of neurodegeneration and depression, anxiety and functional symptoms should be explored. MRI findings- signal changes in the medial temporal lobe, nonconfluent multifocal white matter hyperintense lesions, and isolated white matter microhemorrhages. Novel biomarkers IL-6, MCP-1, and IP-10. <h3>Conclusion</h3> Cognitive symptoms are common after confirmed and assumed COVID exposure. We propose a framework for neuropsychiatric assessment and the use of adjuvant imaging and potential biomarkers.

Successful Recovery of a Fulminant Form of Acute Disseminated Encephalomyelitis (ADEM) with Intravenous Steroids

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system mostly associated with a preceding infection or vaccination. It is characterized by multifocal white matter lesions on neuroimaging. A patient is described who developed a fulminant form of ADEM after a bacterial skin infection. Despite poor prognostic factors and extensive white matter lesions, the patient recovered dramatically under high-dose administration of steroids.

Extended Phenotype in the Transthyretin Tyr77 Familial Amyloid Polyneuropathy

The transthyretin Tyr77 variant of familial amyloid polyneuropathy (FAP) has been identified in a few North American and European patients, but the full spectrum of its clinical manifestations is still not known. We report a 3-generation family of Jewish-Yemenite origin with Tyr77 FAP presenting with atypical features. The affected individuals had sensorimotor and autonomic neuropathy and cardiomyopathy accompanied by prominent dysphagia, hearing loss and asymptomatic carpal tunnel syndrome. Brain MRI in the proband showed multifocal white matter lesions. These features extend the reported Tyr77 phenotype and support the modifying effect of additional factors on the disease expression.

Multifocal leukoencephalopathy and polyneuropathy after 18 years on interferon a

Multifocal leukoencephalopathy and sensory-motor polyneuropathy have not been reported as side-effects of long-lasting interferon α therapy in a single patient. In a 77-year-old man interferon α2b and interferon α2a were administered subsequently but continuously since 1984 for hairy cell leukemia. Since early 2000, left-sided hemi-hypesthesia occurred and the patient developed gait disturbance, proximal weakness of the lower limbs, bilateral stocking-type sensory disturbances, and restless leg syndrome. Repeated cerebral magnetic resonance images showed multifocal T2-hyperintense white matter lesions supratentorially. The nerve conduction velocity of the peroneal and sural nerve was reduced. After exclusion of various differential diagnoses of leukoencephalopathy and application of a screening program for polyneuropathy, central and peripheral nervous system abnormalities were attributed to the long-lasting interferon α therapy. In single patients abnormally long-lasting interferon α therapy may cause multifocal white matter lesions supratentorially and sensory-motor polyneuropathy.

MRI findings in Susac's syndrome.

Susac syndrome (SS) is a self-limited syndrome, presumably autoimmune, consisting of a clinical triad of encephalopathy, branch retinal artery occlusions, and hearing loss. All three elements of the triad may not be present or recognized, and MR imaging is often necessary to establish the diagnosis. To determine the spectrum of abnormalities on MRI in SS. The authors reviewed the MR images of 27 previously unreported patients with the clinical SS triad, and 51 patients from published articles in which the MR images were depicted or reported. All 27 patients had multifocal supratentorial white matter lesions including the corpus callosum. The deep gray nuclei (basal ganglia and thalamus) were involved in 19 (70%). Nineteen (70%) also had parenchymal enhancement and 9 (33%) had leptomeningeal enhancement. Of the 51 cases from the literature, at least 32 had callosal lesions. The authors could not determine the presence of callosal lesions in 18 of these patients, and only one was reported to have a normal MRI at the onset of encephalopathy. The MR scans in SS show a rather distinctive pattern of supratentorial white matter lesions that always involve the corpus callosum. There is often deep gray matter, posterior fossa involvement, and frequent parenchymal with occasional leptomeningeal enhancement. The central callosal lesions differ from those in demyelinating disease, and should support the diagnosis of SS in patients with at least two of the three features of the clinical triad.

Multiple sclerosis: imaging, diagnostic criteria and differential diagnosis

Multiple sclerosis (MS) is the most common demyelinating inflammatory disease of the central nervous system (CNS), presenting with multifocal, disseminated inflammatory lesions referred to as plaques. Magnetic resonance imaging (MRI) typically depicts multiple, round to oval, circumscript lesions predominantly involving periventricular and subcortical white matter, brainstem and cerebellum. More recent investigations have demonstrated that the macroscopically visible plaques only present the tip of the iceberg: Already early in its course, MS causes neuroaxonal damage and diffusely involves the entire brain parenchyma including normal appearing white matter. These changes are reflected by strongly T1w hypointense lesions and atrophy of early onset, by reduction of the neuronal Marker N-acetylaspartate (NAA) on spectroscopy, by a decrease of the magnetization transfer ratio (MTR), by an increased in diffusibility and decreased anisotropy on diffusion-weighted imaging (DWI). MRI imaging is an important tool in the diagnosis of MS by revealing the characteristic spatial and temporal dissemination of the cerebral and spinal manifestations of this disease. Diagnostic criteria increase the diagnostic specificity and allow better differentiation from other diseases with multifocal white matter abnormalities.

Leukoencephalopathy Following CNS Prophylaxis Therapy in Pediatric Leukemia: MR Imaging Findings

Purpose: To evaluate the MR imaging findings and the usefulness of MR imaging in the diagnosis and follow-up of leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia. Materials and Methods: We retrospectively evaluated the MR imaging findings of eight children with white matter abnormalities on MR out of seventeen acute leukemic patients with various neuropsychiatric symptoms who received intrathecal methotrexate administration, with or without cranial irradiation. In all cases, initial MR was performed within a week of the onset of neuropsychiatric symptoms. Follow-up MR was performed one to sixteen months after initial study, and the MR imaging findings were compared with the initial findings. Results: The initial MR imaging findings were classified into three categories: focal or multifocal white matter abnormalities (3/8), and diffuse white matter abnormalities without enhancement (3/8), and diffuse white matter abnormalities with enhancement (2/8). At follow-up MR, diffuse or focal atrophic changes were noted in all children. White matter abnormalities improved in two out of three patients with focal or multifocal white matter abnormalities. In five with diffuse white matter abnormalities, the extent of these showed no significant change, but contrast enhancement was markedly reduced in two children in whom diffuse white matter abnormalities with enhancement had been demonstrated. Conclusion: In pediatric leukemia, the MR imaging findings of leukoencephalopathy following CNS prophylaxis therapy are variable, but are specific with the clinical history of neuropsychiatric symptoms after intrathecal methotrexate administration, with or without cranial irradiation. The MR imaging is valuable in the diagnosis and follow-up of leukoencephalopathy following CNS prophylaxis therapy in pediatric leukemia.

Age-dependent neurologic manifestations of HIV infection in childhood.

Although the neurologic complications of HIV- 1 infection during the first two years of life have been defined, the neurologic features in older children are not so well described. The present report is focused on the age-dependent neurologic presentation of HIV-1 infection. Sixty-two vertically HIV-1 infected children underwent detailed serial evaluations: neurologic assessment, neuropsychological tests, neuroimaging studies, and cerebrospinal fluid analysis. Neurologic involvement was found in 30 patients (48.3%). This population was divided into two groups, exhibiting progressive (83.3%) or nonprogressive (16.6%) neurologic signs and symptoms. In the first group of patients, progressive encephalopathy was distinguished from spastic paraparesis, possibly due to spinal cord involvement. The second group, represented by long-term survivors, requires clinical monitoring due to the possible prognostic value of acquired but presently nonprogressive signs of brain involvement. In contrast with the stereotyped features of the early form of progressive encephalopathy, the late form showed a polymorphic picture, with age-dependent neurologic manifestations. Multifocal white matter alterations and cerebral calcifications (sometimes with delayed onset and progression) were the prominent imaging findings. A correlation between cerebrospinal fluid HIV RNA levels, suggestive of viral replication within the central nervous system, and progressive neurological disease were also found.

Encefalomielitis aguda diseminada en la infancia. Estudio retrospectivo de siete pacientes

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. This study is based on clinical symptoms and diagnostic tests employed. We describe a seven children series indicating the initial neurologic abnormalities, diagnostic tests, treatments used and clinical-neuroradiological evolution. The mean presentation age was 4.1 years. Initial neurologic symptoms were mainly spastic hemi/paraparesis, cerebellous and pyramidal syndrome, consciousness changes, meningeal signs, seizures and cranial nerve palsies. The cerebrospinal fluid was abnormal in four patients with positive serologic tests in two of them (Coxsackie B). Electrophysiological studies were affected in 50%. MRI findings consisted of multifocal supratentorial white matter lesions. Clinical evolution revealed a progressive improvement with resolution after two months. Follow-up was made between six months and five years. The treatment was based on aciclovir and corticosteroids. ADEM runs a monophasic course of progressive neurologic abnormalities. Diagnosis is based on suggestive clinical and neuroimaging findings. Generally speaking, MRI showed resolution of multifocal lesions in conjunction with clinical improvement.

Diagnostic criteria and clinical procedures in HIV-1 associated progressive multifocal leukoencephalopathy

The diagnosis of definite progressive multifocal leukoencephalopathy (PML) has been a neuropathological domain. We reviewed all Human Immunodeficiency Virus Type 1 (HIV-1) seropositive patients in our institution between 01.01.1989 and 31.12.1994 and identified 20 823 cases with PML by clinical and imaging criteria. Diagnosis was neuropathologically confirmed in 5 cases. Diagnostic criteria included rapid onset (<2 weeks) of multifocal neurological signs and symptoms, advanced immunosuppression and asymmetric uni- or multifocal white matter lesions without mass effect, contrast enhancement or cortical atrophy in magnetic resonance imaging (MRI). The overall incidence of PML was stable over the observation period (≅2.5%). The mean age at onset (41.7 years) was significantly lower compared to HIV-1 seronegative PML patients (peak in the sixth decade of life), male patients prevailed (100%). Mean survival (3.9 months) was extremely short. Human polyoma virus JC (JCV) polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) demonstrated a considerable rate of possible cerebral co-infection with HIV-1 and JCV as well as subclinical infection with JCV. Therefore demonstration of JCV deoxyribonucleic acid by PCR in the CSF alone is not sufficient for clinical PML diagnosis. We present diagnostic criteria on the basis of epidemiological, neuroradiological and CSF parameters that allow us to make the clinical diagnosis of PML. Although quick and safe, routine stereotactic brain biopsy is not necessary to confirm the diagnosis.

Nervous system manifestations in HIV infected children

In 34 perinatally HIV infected children time of manifestation, type and treatability of neurologic disorders were investigated for a period of 7 years (1987-1994). Neurological investigations were done every 6 months; EEG and MRI/CT were examined initially in the asymptomatic stage and were repeated when neurologic Symptoms occurred. Zidovudine therapy was started after onset of symptoms, dosage was raised, when treatment with Zidovudine had already begun (600-720 mg/m2/day). Various neurological manifestations were seen in 4 of 12 patients in stage B (33%) and in 11 of 14 children in AIDS (80%). 7 of the 14 AIDS-patients (50%) developed a subacute progressive course or progressive plateau course and 4 of 14 (30%) a static course of encephalopathy. Pathological changes in EEG were seen in 54% of investigated patients with neurological deficits. Neuroimaging revealed pathological findings in all symptomatic subjects, 6 of 11 patients in AIDS (55%) has a severe general cerebral atrophy and multifocal white matter lesions. Zidovudine had a positive temporary effect from 6 to 12 months in 5 of 11 treated patients (45%). At present a thorough neurological examination is the most sensitive method to detect neurological impairment in HIV infected children. In most cases CT/MRI scan provides information about the course of the encephalopathy. Antiretroviral therapy has a limited benefit, if neurologic symptoms start after the second year of life.

Multifocal white matter lesions

There is a long differential diagnosis for multifocal white matter lesions on MR. The most common causes are prominent Virchow-Robin spaces, white matter ischemic change, and multiple sclerosis, but many other causes have been reported. Most of these are related to vascular or other demyelinating etiologies, but infectious/inflammatory disease, trauma, and neoplastic and other unusual causes may also be responsible. Typical imaging features of the more common multifocal white matter disorders are outlined, and the rarer causes are discussed briefly. An approach to imaging differential diagnosis is given, with emphasis on the differences between white matter ischemic lesions and multiple sclerosis.

Severe cerebellar atrophy following acute cerebellitis

The clinical course and serial magnetic resonance imaging findings of a 4-year-old girl with acute cerebellar ataxia due to acute cerebellitis are described. Multifocal white matter lesions visualized by magnetic resonance imaging in both cerebellar hemispheres in the acute phase disappeared in the convalescent phase. Cerebellar signs became less prominent within 2 weeks, but mild ataxic gait remained. During the follow-up period of 32 months, there was a gradual development of cerebellar atrophy along with a recurrence of cerebellar ataxia.

GUINEA-PIG SPINAL-CORD AS A MODEL FOR THE STUDY OF LATE RADIATION-INJURY AND REPAIR

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.