Extensive White Matter Lesions Research Articles

Cerebral and Extracerebral Vasoreactivity in Patients With Different Clinical Manifestations of Cerebral Small-Vessel Disease: Data From the Significance of Hemodynamic and Hemostatic Factors in the Course of Different Manifestations of Cerebral Small-Vessel Disease Study.

Endothelial dysfunction has been implicated in the pathogenesis of cerebral small-vessel disease (SVD). Little is known about the relationship between SVD and measures of endothelium-dependent vasodilatation and cerebral vasomotor reactivity. The aim of this study was to evaluate cerebral and extracerebral endothelial dysfunction in patients with different manifestations of SVD and to assess the relationship between endothelial dysfunction and radiologic markers of SVD. The vasomotor reactivity reserve (VMRr), breath-holding index (BHI) of the middle cerebral arteries, and brachial artery flow-mediated dilatation (FMD) were measured with ultrasound techniques in 90 patients (30 in each group) older than 60 years with extensive white matter lesions (Fazekas grade ≥ 2) with a history of lacunar stroke, vascular dementia, or parkinsonism and 30 individuals with normal magnetic resonance imaging findings (control group). All groups were matched for age, sex, hypertension, and diabetes. The mean age ± SD (71.8 ± 3.4 versus 71.7 ± 3.4 years), sex distribution, and prevalence of the main vascular risk factors were similar in the SVD and control groups. The VMRr (56.6% ± 18.3% versus 77.1% ± 16.9%), BHI (0.8 ± 0.3 versus 1.1 ± 0.4), and FMD (5.8% ± 4 versus 12.1% ± 5.2%) were severely impaired in the SVD groups compared to the control group (P < .01). The vascular responses to all tests was similar in the SVD groups, but they were significantly decreased in patients with severe white matter lesions, marked brain atrophy, and enlarged perivascular spaces. This study was the first that simultaneously evaluated cerebral and extracerebral vasodilator responses in a well-phenotyped cohort of patients with lacunar stroke, vascular dementia, or parkinsonism. The VMRr, BHI, and FMD were more severely impaired in patients with SVD, regardless of its clinical manifestation, than in control participants. All measures were significantly lower in patients with severe white-matter lesions, brain atrophy, or enlarged perivascular spaces.

Different features between pediatric-onset and adult-onset patients who are seropositive for MOG-IgG: A multicenter study in South China

BackgroundImmunoglobulin against myelin oligodendrocyte glycoprotein (MOG-IgG) is a potential demyelinating disease-associated autoantibody. Whether clinical features of MOG antibody-associated demyelinating diseases change with age remains unclear. ObjectTo investigate the different clinical features between pediatric-onset and adult-onset MOG-IgG-seropositive patients in a relatively large cohort. MethodsA total of 816 consecutive patients with suspected demyelinating disease were prospectively enrolled from three tertiary academic centers in South China from February 2016 to December 2016. Sixteen pediatric-onset cases (≤14 years old) and 34 adult-onset cases (>14 years old) seropositive for MOG-IgG were identified. Differences in clinical features between the two groups were investigated. ResultsThere was a significant difference in the cumulative incidence of first relapse among the two groups (P = .008). Cerebral symptoms were significantly higher in pediatric-onset patients than in adult-onset patients, either at disease onset (pediatric-onset group, 10/16(62.5%); adult-onset group, 8/34(23.53%); P = .007) or throughout the course of disease (pediatric-onset group, 11/16(68.8%); adult-onset group, 10/34(29.4%); P = .009). Optic nerve symptoms were more common in adult-onset groups, but no significant difference was found between the two groups. A significantly higher rate of pediatric-onset patients (9/16, 56.3%) met the acute disseminated encephalomyelitis criteria compared with adult-onset patients (2/34, 5.9%) (P = .0003), and isolated optic neuritis was mainly diagnosed in adult-onset patients (pediatric-onset group, 2/16(12.5%); adult-onset group, 14/34(41.2%); P = .043). The MOG-IgG titer showed a significant positive correlation with total protein levels in cerebrospinal fluid, but only in adult-onset patients (r = 0.95; P = .0004). On magnetic resonance imaging, extensive white matter lesions were observed in both groups, and the number was much higher in pediatric-onset (7/15, 46.7%) than in adult-onset patients (4/29, 13.8%) (P = .043). At the last follow-up, more pediatric-onset patients (10/16, 62.5%) experienced complete recovery (EDSS 0.0 at last follow up) compared with adult-onset patients (9/34, 26.5%) (P = .014). ConclusionsDistinctive features are present between pediatric-onset and adult-onset patients with MOG-IgG. Further studies are required to determine the different underlying pathogenesis of MOG antibody at different ages.

Four years clinical follow-up and review analysis in a novel IBA57 mutation associated multiple mitochondrial dysfunction syndrome

Objective To investigate the clinical, imaging and IBA57 gene mutation features in a Chinese patient with multiple mitochondrial dysfunction syndrome, and to evaluated the effect of comprehensive rehabilitation. Methods The clinical data of 1 case of multiple mitochondrial dysfunction syndrome with IBA57 mutation in Department of Rehabilitation, Anhui Provincial Children′s Hospital were analyzed.IBA57white matter malnutritionandIBA57leukodystrophywere used as the key words, to search for papers which were included in CNKI, the knowledge service platform of Wanfang Data, and biomedical literature database (PubMed) from its establishment to February 2017.The clinical, imaging and gene mutation characteristics of children with IBA57 gene mutation were summarized. Results Children, male, four years and 8 months, formovement disorders for nearly 4 years, repeated seizures 1 and a half yearsin February 2017 hospitalized again.The boy was admitted into hospital when he was one year of age because of motor and cognitive disorder after fever, Disease was development, The skull MRI showed multiple abnormal signal in bilateral frontal occipital lobe and semi-oval center white matter.Cognitive and verbal improvement was better, and the motor function gradually improved after repeated rehabilitation in our hospital, skull MRI showed that multiple abnormalities were reduced in bilateral frontal occipital lobe and semi-oval center white matter.However, The boy presented twitch when he was three years and 2 months old.Skull MRI showed that multiple abnormal signal increased in bilateral forehead occipital lobe and semi-oval center white matter in four years and 3 months and 6 months of age.The child was diagnosed with white matter disease after multiple hospitalizations, and c. 286T>C(p.Tyr86His)and c. 1053G>A(p.Trp351*)were found in the IBA57 gene through exome sequencing analysis, as the 2 mutations constituted complex heterozygous mutation.The former was inherited from the mother, and the mutation was missense mutation, so the protein structure was predicted to be harmful; the latter was inherited from the father, and the mutation was nonsense mutation, which could lead to the coding protein truncation, and this was never reported before.The child was diagnosed as multiple mitochondrial dysfunction syndrome type 3, followed by treatment with high-dose coenzyme Q10, ATP, compound vitamin B and others.While taking levetiracetam and topiramate antiepileptic, and family rehabilitation, his condition was stable. Conclusion The extensive white matter lesions presented in the child may be caused by mitochondrial disease with IBA57 gene mutation. Key words: IBA57; Multiple mitochondrial dysfunction syndrome; White matter; Epilepsy; Mitochondria

Development and validation of a priori risk model for extensive white matter lesions in people age 65 years or older: the Dijon MRI study

ObjectivesThe objective was to develop and validate a risk model for the likelihood of extensive white matter lesions (extWML) to inform clinicians on whether to proceed with or forgo diagnostic...

Twenty-four-hour blood pressure monitoring in Alzheimer’s disease patients with or without small vessel diseases

Background: Lack of nocturnal blood pressure (BP) dipping has been reported to be positively associated with vascular dementia or extensive white matter lesions. However, few studies have performed for Alzheimer’s disease (AD).

Diagnosis of sepsis associated encephalopathy: a retrospective analysis of 6 patients

Objective To investigate whether the presence of infection in a case series with coma would predict sepsis associated encephalopathy(SAE). Methods From Jan 2013 to Oct 2014, we used the criteria of systemic inflammatory response syndrome (SIRS) positive sepsis with encephalopathy and retrospective diagnosed a comatose case series with infection and from a tertiary teaching hospital intensive care unit (ICU). Results Among 6 comatose patients with evidence of infection, 3 cases were secondary infection after hemorrhagic stroke, 1 case was secondary infection after trauma, and the other 2 cases were primary infection.All patients met the diagnosis of SIRS-positive sepsis with encephalopathy.Among them, the presence of SIRS 3 criteria was in 2 cases, four criteria in 4 cases.All patients with severe brain failure (100%), in addition to 5 cases with acute respiratory failure caused by lung injury, one case with acute liver failure.Brain imaging confirmed that the delayed vasogenic edema was in two cases(33.3%), the cerebral ischemic lesions in four cases(66.7%). The ischemic lesion included 1 patient with minor infarcts and 1 case with mild white matter lesions, and with a good prognosis.The other two ischemic cases included multifocal leukoencephalopathy with central pontine myelinolysis in 1 case and extensive white matter lesions in 1 case, eventually with a poor prognosis. Conclusion SAE is a common critically illness, the use of the new classification criteria of sepsis is helpful in the diagnosis of sepsis associated encephalopathy. Key words: Sepsis; Sepsis associated encephalopathy; Coma; Systemic inflammatory response syndrome; Organ failure; Imaging

White matter lesions in FTLD: distinct phenotypes characterize GRN and C9ORF72 mutations.

Frontotemporal lobar degeneration (FTLD) has a high frequency of genetic forms; the 2 most common are GRN (progranulin) and C9ORF72 mutations. Recently, our group reported extensive white matter (WM) lesions in 4 patients with FTLD caused by GRN mutation, in the absence of noteworthy cardiovascular risk factors,(1) in line with other studies in GRN mutation carriers.(2,3) Here we compared the characteristics of frontal WM lesions in patients with behavioral variant of FTLD (bv-FTLD) caused by GRN and C9ORF72 mutations.

White matter integrity and cognitive dysfunction: Radiological and neuropsychological correlations.

Cerebral white matter (WM) is comprised of nerve fibers interconnecting neurons in the cerebral cortex or the deep structures. With advancing age, WM frequently shows hyperintense lesions in T2-weighted or fluid-attenuated inversion recovery images in both the periventricular and deep WM. Patients with these WM lesions might manifest a variety of symptoms, such as parkinsonism, cognitive impairment, depression and apathy, when these WM lesions become sufficiently confluent and diffuse. However, there are inconsistencies with respect to their clinical significance, because patients with extensive WM lesions might remain asymptomatic. The present review focuses on the pathological mechanism underlying why the loss of integrity of nerve fibers in the WM induces neuropsychological symptoms.

Left ventricular geometry and white matter lesions in ischemic stroke patients

Abnormal left ventricular (LV) geometry is associated with extracardiac organ damage in patients with hypertension. The aim of this study was to determine the relationship between LV geometry and white matter lesions (WMLs) in ischemic stroke patients. We retrospectively analyzed data from 155 patients (median age 62; 49.8% male) with mild ischemic stroke (median National Institutes of Health Stroke Scale score 4) who underwent brain magnetic resonance imaging and echocardiography. Patients were categorized into four groups: normal LV geometry, concentric remodeling, eccentric left ventricular hypertrophy (LVH) and concentric LVH. WMLs were graded using the Fazekas scale on fluid-attenuated inversion recovery images. Extensive WMLs were defined as a Fazekas score > 2. Extensive WMLs were more prevalent in patients with concentric LVH, eccentric LVH and concentric remodeling than in those with normal LV geometry. After adjusting for hypertension, age, diabetes mellitus, hypercholesterolemia, glomerular filtration rate and ischemic heart disease, patients with concentric remodeling [odds ratio (OR) 3.94, 95% confidence interval (CI) 1.26–12.31, p = 0.02] and those with concentric LVH (OR 3.69, 95% CI 1.24–10.95, p = 0.02), but not patients with eccentric LVH (OR 2.44, 95% CI 0.72–8.29, p = 0.15), had higher risk of extensive WMLs than patients with normal LV geometry.

A novel mouse model of subcortical infarcts with dementia.

Subcortical white matter (WM) is a frequent target of ischemic injury and extensive WM lesions are important substrates of vascular cognitive impairment (VCI) in humans. However, ischemic stroke rodent models have been shown to mainly induce cerebral infarcts in the gray matter, while cerebral hypoperfusion models show only WM rarefaction without infarcts. The lack of animal models consistently replicating WM infarct damage may partially explain why many neuroprotective drugs for ischemic stroke or VCI have failed clinically, despite earlier success in preclinical experiments. Here, we report a novel animal model of WM infarct damage with cognitive impairment can be generated by surgical implantation of different devices to the right and left common carotid artery (CCA) in C57BL/6J mice. Implantation of an ameroid constrictor to the right CCA resulted in gradual occlusion of the vessel over 28 d, whereas placement of a microcoil to the left CCA induced ∼50% arterial stenosis. Arterial spin labeling showed a gradual reduction of cerebral blood flow over 28 d post operation. Such reductions were more marked in the right, compared with the left, hemisphere and in subcortical, rather than the cortical, areas. Histopathological analysis showed multiple infarct damage in right subcortical regions, including the corpus callosum, internal capsule, hippocampal fimbria, and caudoputamen, in 81% of mice. Mice displaying such damage performed significantly poorer in locomotor and cognitive tests. The current mouse model replicates the phenotypes of human subcortical VCI, including multiple WM infarcts with motor and cognitive impairment.

Abstract T P178: Cerebral Blood Flow and Metabolism Associated with Cerebral Microbleeds in Patients with Non-cardioembolic Stroke Without Major Cerebral Arterial Stenosis

Background and Purpose: Cerebral microbleeds (CMBs) are associated with not only higher age but also extensive white matter lesions (WMLs), indicating that CMBs could be a reflection of microangiopathy. CMBs have not yet been examined in association with cerebral blood flow (CBF) and metabolism. The purpose of this study was to clarify the relationships of CMBs with WMLs volume, and CBF and metabolism in patients with ischemic stroke. Methods: We enrolled 19 patients who had past history of non-cardioembolic stroke without severe stenosis (&gt;50%) in major cerebral arteries (69±7 years, 9 women). We measured WMLs volume and counted the number of CMBs on a 1.5-T magnetic resonance imaging (MRI) scanner. CBF, cerebral blood volume, oxygen extraction fraction and cerebral metabolic rate of oxygen were measured with 15 O-labeled gas positron emission tomography (PET). We set 36 regions of interest (ROIs) in the cortex-subcortex regions, basal ganglia and centra semiovale in each patient on MRI. MRI was superimposed on PET images and 4 parameters of each ROI were calculated. Results: CMBs existed in 14 out of 19 patients (median 5; range 0-39). Patients were divided into 2 groups according to the number of CMBs; less than 5 as the group I (n=9) and 5 or more as the group II (n=10). WMLs volume of the group II was larger than that of the group I (median 38.4 with range of 25.1-91.5 vs. 10.0 with 4.2-73.4 ml, p=0.020). In the centra semiovale, CBF of the group II was significantly lower than that of the group I (12.5±2.5 vs. 15.7±3.5 ml/100g/min, p=0.031). In the other regions, there were no significant differences in all 4 parameters of PET between the 2 groups. Conclusions: We showed that the increases in the number of CMBs could indicate cerebral ischemia in the deep white matter of patients with non-cardioembolic stroke without major cerebral arterial stenosis.

Adult-onset vanishing white matter disease as differential diagnosis of primary progressive multiple sclerosis: A case report

We report the case of a 42-year-old woman with a slowly progressive cerebellar syndrome. In contrast to a relatively mild clinical presentation, the magnetic resonance imaging (MRI) showed extensive leukencephalopathy with cystic degeneration. Initially primary progressive multiple sclerosis (PPMS) was suspected. Additional diffusion-weighted imaging revealed restricted diffusion in the white matter lesions with a reduced apparent diffusion coefficient. Genetic testing showed vanishing white matter disease (VWM) with c.260C>T EIF2B3 mutation. In conclusion, in cases with relatively mild symptoms and extensive white matter lesions, adult-onset VWM should be considered as differential diagnosis of PPMS and diffusion-weighted imaging may be helpful to identify suspected cases.

Homozygous TREM2 mutation in a family with atypical frontotemporal dementia

TREM2 mutations were first identified in Nasu-Hakola disease, a rare autosomal recessive disease characterized by recurrent fractures because of bone cysts and presenile dementia. Recently, homozygous and compound heterozygous TREM2 mutations were identified in rare families with frontotemporal lobar degeneration (FTLD) but without bone involvement. We identified a p.Thr66Met heterozygous mutation in a new consanguineous Italian family. Two sibs had early onset autosomal recessive FTLD without severe bone disorders. Atypical signs were present in this family: early parietal and hippocampus involvement, parkinsonism, epilepsy, and corpus callosum thickness on brain magnetic resonance imaging. This study further demonstrates the implication of TREM2 mutations in FTLD phenotypes. It illustrates the variability of bone phenotype and underlines the frequency of atypical signs in TREM2 carriers. This and previous studies evidence that TREM2 mutation screening should be limited to autosomal recessive FTLD with atypical phenotypes characterized by: (1) a very young age at onset (20–50 years); (2) early parietal and hippocampal deficits; (3) the presence of seizures and parkinsonism; (4) suggestive extensive white matter lesions and corpus callosum thickness on brain magnetic resonance imaging.

Patterns of Cognitive Performance in Subcortical Ischemic Vascular Disease (SIVD)

Subcortical ischemic vascular disease (SIVD) is characterized by extensive white-matter lesions and lacunar infarcts in deep gray matter. The aim of this study was to investigate patterns of cognitive impairment in patients with SIVD. In a retrospective analysis, the authors compared the cognitive performance of 58 patients meeting MRI-defined criteria for SIVD (26 women; 47.3%) with age- and gender-matched control subjects. SIVD patients showed impairments in measures of verbal fluency, verbal memory, speed of cognitive processing, and divided attention. There were no significant differences in constructional praxis, figurative memory, verbal recognition memory, or semantic processing.

Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59

Spinal cord pathology with inflammatory, demyelinating lesions spanning three or more vertebral segments is a characteristic feature of neuromyelitis optica (NMO). NMO pathogenesis is thought to involve binding of immunoglobulin G anti-aquaporin-4 autoantibodies (NMO-IgG) to astrocytes, causing complement-dependent cytotoxicity (CDC) and secondary inflammation, demyelination and neuron loss. We investigated the involvement of CD59, a glycophosphoinositol (GPI)-anchored membrane protein on astrocytes that inhibits formation of the terminal C5b-9 membrane attack complex. CD59 inhibition by a neutralizing monoclonal antibody greatly increased NMO-IgG-dependent CDC in murine astrocyte cultures and ex vivo spinal cord slice cultures. Greatly increased NMO pathology was also found in spinal cord slice cultures from CD59 knockout mice, and in vivo following intracerebral injection of NMO-IgG and human complement. Intrathecal injection (at L5–L6) of small amounts of NMO-IgG and human complement in CD59-deficient mice produced robust, longitudinally extensive white matter lesions in lumbar spinal cord. Pathology was most severe at day 2 after injection, showing loss of AQP4 and GFAP, C5b-9 deposition, microglial activation, granulocyte infiltration, and demyelination. Hind limb motor function was remarkably impaired as well. There was partial remyelination and recovery of motor function by day 5. Our results implicate CD59 as an important modulator of the immune response in NMO, and provide a novel animal model of NMO that closely recapitulates human NMO pathology. Up-regulation of CD59 on astrocytes may have therapeutic benefit in NMO.

Two cases of multinodular and vacuolating neuronal tumour

An unusual multinodular and vacuolating neuronal tumour (MVNT) has been described in the cerebral hemispheres of ten patients with adult-onset seizures. We report the findings in two cases with similar features, a surgical resection and the other an autopsy specimen.Case 1, a 34-year-old female, underwent surgical resection for a multinodular non-enhancing frontal white matter lesion causing intractable epilepsy. Case 2, presented with motor neurone disease (MND) at the age of 71 and MRI scanning revealed extensive multinodular non-enhancing white matter lesions in the temporal lobe. There was no history of epilepsy and post mortem histology confirmed MND.Macroscopically multiple small grey well-formed, discrete and coalescent nodules were seen in the deep cortex and subcortical white matter. On histology, mature-looking neurons with large cytoplasmic vacuoles were distributed in a fibrillary background, where vacuoles were also noted. In the resected tumour scattered oligodendroglia-like cells were present. No ganglion cells were seen. The vacuolated cells exhibited immunopositivity for synaptophysin, HuC/HuD and p62 but were negative for NeuN, neurofilament, GFAP, IDH1, nestin and CD34. Electron microscopy showed non-membrane bound cytoplasmic vacuoles in the neurons and in some neuronal processes. The seizures recurred in Case 1.Some clinicopathological features of this lesion suggest a possible relationship with dysembryoplastic neuroepithelial tumour (DNT) although the morphological features are not typical of DNT. Case 2 demonstrates that MVNT may remain asymptomatic.

Neuromyelitis optica spectrum disorders accompanying subarachnoid hemorrhage and reversible white matter lesions

A 48-year-old man was admitted to Tomakomai City Hospital, Tomakomai, Japan, because of intractable hiccups and nausea, and orthostatic hypotension. Brain magnetic resonance imaging findings showed a dorsal medullary lesion. Respiratory failure occurred, and he underwent tracheotomy and mechanical ventilation when magnetic resonance imaging showed subarachnoid hemorrhage in addition to enlarged medullary lesions. Serum anti-aquaporin-4 antibody was positive and the cerebrospinal fluid was bloody. We diagnosed meuromyelitis optica spectrum disorders complicating subarachnoid hemorrhage. He was treated with a steroid. Although extensive white matter lesions occurred transiently, the patient was discharged from the hospital when he became able to walk with the use of the walker on the 52nd day. We suggest that the subarachnoid hemorrhage and transient white matter lesions were associated with vascular damage associated with the meuromyelitis optica spectrum disorders.

Plaque-like demyelination in acute disseminated encephalomyelitis (ADEM) – an autopsy case report

The pattern of demyelination in the scant autopsy literature on acute disseminated encephalomyelitis (ADEM) is described as perivenous sleeves. We report an unusual neuropathological presentation of ADEM, also known as postinfectious or perivenous encephalomyelitis. A 19-yearold female patient presented with headache and myalgias, followed by subacute onset of lethargy, confusion, left hemiparesis and dysphasia after an interval of 4 - 5 days. On MRI, extensive subcortical white matter lesions were seen and a diagnosis of ADEM was made after other causes were excluded. The patient received intravenous methylprednisolone and plasma exchange. Neurological symptoms remained stable over the length of the hospital stay (1 month). The patient passed away due to non-neurologic causes. On autopsy, the brain showed extensive, confluent, plaque-like demyelinating lesions with a striking selectivity for the subcortical white matter sparing the U-fibers. No lesions were discernible in the cortex, the deep grey matter, the cerebellum, the spinal cord or the optic nerves on LFB-stained sections. Only one lesion extended to the periventricular area in the right occipital lobe. Some lesions had a scalloped border and foci of inhomogeneous demyelination, suggestion coalescence of smaller lesions. Histologically, all lesions were of the same age, coupling near complete demyelination with relative preservation of axons, along with scant perivascular lymphohistiocytic cuffing, dense infiltration by foamy macrophages, and prominent gliosis. The morphology of individual demyelinating< lesions is indistinguishable from the lesions in a new onset case of multiple sclerosis (MS) and adds to the autopsy literature on overlapping neuropathological findings in ADEM and multiple sclerosis.

Unusual epileptic deterioration and extensive white matter lesion during treatment in Wilson’s disease

BackgroundWilson’s disease (WD) is a genetic disorder which can be controlled fairly well with decupuration therapy. However, symptoms, on rare occasions, can worsen even when WD is being treated. Herein, we report a case involving unusual neurological deterioration during decupuration therapy for WD.Case presentationA 28-year-old man was diagnosed with WD 13 years prior to his clinical visit; however, his drug compliance has been poor over the years. He was treated with trientine because tremors and dysarthria have presented in recent years. However, dysarthria and dystonia developed in his limbs, which were worse on the right side and had been aggravated for several weeks despite good drug compliance. His symptoms were fluctuating. It was initially misdiagnosed as dystonia; although, it turned out to be a seizure due to cortical degeneration. These symptoms were completely resolved with antiepileptic drugs. Moreover, the cortical enhancement of bifrontal degeneration has disappeared on the MRI.ConclusionThis case showed unusual epileptic neurologic deterioration due to cortical degeneration during decupuration therapy. Seizures in WD can easily be mistaken as part of dystonia. However, the fluctuating symptoms suggest a seizure.

A new CSF1R mutation presenting with an extensive white matter lesion mimicking primary progressive multiple sclerosis

HDLS (Hereditary Diffuse Leukodystrophy with Spheroids) is a hereditary leukodystrophy whose main clinical manifestations include parkinsonism, spasticity, and ataxia. Genetic defects in the colony-stimulating factor 1 receptor (CSF1R) gene have been reported in many HDLS cases. The present report describes a new missense mutation Arg777Gln involving exon 18 of the CSF1R gene in a sporadic patient presenting with tumor-like lesions mimicking primary progressive multiple sclerosis. The patient was initially diagnosed with a progressive variant of multiple sclerosis and received inadequate treatments. Although most HDLS cases have a positive family history, this disease should also be suspected in sporadic patients showing unusual white matter lesions at MRI.