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Vanishing White Matter Disease (VWMD) is a rare autosomal recessive leukoencephalopathy . The classical presentation is characterized by a severe cerebellar ataxia, spasticity, neurological deterioration with a chronic progressive course and episodes of acute neurological deterioration after stress conditions.We report a 52-year-old man with VWMD and atypical features who manifested two major events of transient aphasia eleven years apart with complete recovery in 48 hours. No cognitive decline was present. Brain MRI revealed typical aspects of VWMD including diffuse leukoencephalopathy with relative sparing of U-fibers. We identified the presence of c.592G>A (p.Glu198Lys) and c.1360 C>T (p.Pro454Ser) mutations in EIF2B5.

Hereditary diffuse leukoencephalopathy with axonal spheroids demonstrates clinical and neuroimaging heterogeneity.

A 47-year-old man presented to clinic with progressive right-hand bradykinesia and shuffling gait for 8 months. He was diagnosed with parkinsonism. Brain MRI demonstrated diffusion-weighted imaging (DWI)–hyperintense signal involving bilateral corona radiate (figure 1) and T2-weighted MRI showed white matter changes (figure 2). Colony-stimulating factor 1 receptor ( CSF1R ) gene sequencing revealed the pathogenic variant c.2381T>C(p.Ile794Thr), confirming the diagnosis of hereditary diffuse leukoencephalopathy with spheroids.1 The patient was treated with levodopa and selegiline with minimal response.2

We report a sporadic case of hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) confirmed by biopsy and colony-stimulating factor 1 receptor ( CSF1R) sequencing. A 28-year-old woman developed progressive spastic gait and dysarthria. Brain T2/FLAIR-weighted magnetic resonance imaging showed bilateral high signal intensity lesions in the parietal deep white matter, which subsequently extended anteriorly. Biopsied brain specimens demonstrated demyelinated white matter tissue with axonal spheroids infiltrated with foamy macrophages, and CD8+ and CD4+ T cells. She had a heterozygous mutation, c.2381T>C (p.782 Ile>Thr), in CSF1R. This is the first genetically proven case of HDLS mimicking primary progressive multiple sclerosis.

Background Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal dominant disorder characterized by cerebral white matter degeneration and caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. Involvement of the optic nerves in hereditary diffuse leukoencephalopathy is rare. Case presentation We report the case of a 30-year-old Chinese woman with HDLS, who carried a heterozygous c.2345 G > A (p.782Arg > His) mutation in exon 18 of CSF1R. She developed a gradual decline in motor ability, as well as cognitive and visual function, over the course of 4 months. Brain T2 fluid-attenuated inversion recovery-weighted magnetic resonance imaging revealed high signal lesions in the bilateral frontoparietal and periventricular deep white matter. Optical coherence tomography showed that the right peripapillary retinal nerve fiber layer was atrophic in the temporal quadrant while the left peripapillary retinal nerve fiber layer was thin in the temporal superior quadrant. Conclusions A diagnosis of HDLS should be considered in patients with white matter lesions and optic nerves injury upon magnetic resonance imaging that mimics progressive multiple sclerosis.

Two consanguineous siblings presented with developmental regression and emerging spasticity. Cranial magnetic resonance imaging in both showed diffuse leukoencephalopathy. Further investigation established the siblings as having complex 1 deficiency consequent to a novel homozygous mutation in NDUFV1, a nuclear-encoded subunit of complex 1. Diffuse leukoencephalopathy may be a presentation of complex 1 deficiency.

A 52-year-old right-handed man reported 2 years of progressive word-finding difficulties. He noticed hesitations when retrieving words and difficulty writing and calculating while working in his carpentry business. He was taking pravastatin for hyperlipidemia. Memantine was started prior to our clinical evaluation, and had no measurable effect. He had a great aunt with late-life amnestic dementia, his father died at age 59 years from lung cancer, and his mother died at age 75 of unknown causes. He had 18 years of education and no history of learning disabilities.

Department of Neurology, Ludwig-Maximilians-Universitat, Munich, Germany Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universitat, Munich, Germany Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tubingen, Germany German Research Center for Neurodegenerative Diseases (DZNE), University of Tubingen, Germany CeGaT GmbH, Center for Genomics and Transcriptomics, Tubingen, Germany Department of Neurosurgery, Ludwig-Maximilians-Universitat, Munich, Germany Department of nuclear medicine, Ludwig-Maximilians-Universitat, Munich, Germany Department of Neuroradiology, Ludwig-Maximilians-Universitat, Munich, Germany Department of Child Neurology, VU Medical Center, Amsterdam, The Netherlands German Research Center for Neurodegenerative Diseases (DZNE), Ludwig-Maximilians-Universitat, Munich, Germany

Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a neurodegenerative disease clinically characterized by slowly progressive cognitive decline and motor dysfunction. Neuropathology shows diffuse degeneration in the white matter, with prominent presence of widespread axonal spheroids. To investigate the mechanism underlying HDLS neurodegeneration, we characterized spheroids and examined their development in the degenerated white matter. Analysis revealed that the spheroids are an early neuropathological manifestation in the white matter degeneration and involve axonal component proteins and α-synuclein. The development of spheroids facilitates in initiating neurodegeneration in HDLS.

Cerebral amyloid angiopathy (CAA) is a well-established cause of brain hemorrhage in the elderly. The association of CAA with other structural brain lesions is less well known. We report a 69 year old diabetic woman with dementia of acute onset Cranial CT and MRI showed diffuse leukoencephalopathy with predominant right parieto-occipital distribution. Pathological study demonstrated severe CAA. We review the association of CAA with dementia and leukoencephalopathy.

We read with interest the report by Oboudiyat et al.1 of a patient with diffuse leukoencephalopathy with spheroids (DLS) presenting with nonfluent aphasia. We followed a left-handed patient presenting in his mid-40s with rapidly progressive stuttering, apraxia of speech, emotional lability, tremor, and unsteady gait. Neurologic examination showed impaired word fluency and sentence …

Cystic leukoencephalopathy with megalencephaly is a newly described entity with mild clinical involvement. Patients suffer from developmental problems and seizures in childhood. Progression is gradual into adulthood. Typical magnetic resonance imaging findings include subcortical cysts and diffuse leukoencephalopathy. The etiology is unknown with possibly autosomal-recessive inheritance. We present two pairs of siblings with this disease and emphasize the characteristic and variable patterns even within the same family. (J Child Neurol 2000;15:690-693).