A case progressive dementia developed after repeated head trauma

A 46-year-old man who developed progressive dementia after repeated head trauma was reported. At the age of 30 and 36, he encountered traffic accidents and suffered from blows to his head. At 37 years old, he noticed impairment of memory and comprehension. At 41 years old, he was observed to become easily angered. These symptoms were slowly progressive, and at age 46 he was examined by us. He had no particular family history of dementia. Neurological examination revealed a disturbance of cognitive ability. The brain CT and MRI showed marked atrophy of the cerebral cortex, especially in the frontal and temporal lobes without any demonstrable lesions in the white matter. A single photon emission computed tomography (SPECT) using inhalation of 133Xenon disclosed hypoperfusion of the cerebral blood flow localized in the bilateral frontal and parietal lobes. He was supposed to suffer from juvenile Alzheimer's disease which might have developed after repeated head trauma. One similar case had been reported as a posttraumatic premature Alzheimer's disease. Finally, we discussed other causes of dementia including metabolic, infectious and vascular diseases. The present case also suggests that head trauma might be one of the provoking or promoting factors of Alzheimer's disease.     

Low signal intensity and increased anisotropy on magnetic resonance imaging in the white matter lesion after head trauma: unrecognized findings of diffuse axonal injury

We report on a four-year-old girl with head trauma caused by a motor vehicle accident. She presented with delirium, oculomotor palsy and ptosis in her left eye, left hemiparesis, and pyramidal signs in all extremities. Computed tomography on the day of admission showed diffuse cerebral edema with right-sided predominance. Magnetic resonance images on day 3 of admission showed lesions of diffuse axonal injury and contusion in the corpus callosum and right occipital and bilateral temporal lobes. There was a low-intensity lesion in the white matter of the right hemisphere on T2-weighted images, fluid-attenuated inversion recovery, T2()-weighted images, apparent diffusion coefficient maps and diffusion-weighted images. This low-intensity lesion disappeared by day 7, and a transient brain atrophy in the right hemisphere appeared on day 28. The low signal intensity in the cerebral white matter was apparently different from that associated with contusion and typical diffuse axonal injury, and might represent a late-onset accumulation of non-heme iron and free radicals in the white matter after head trauma.     

Leukoencephalopathy with intracranial calcifications and cysts in an adult: Case report and review of literature

Leukoencephalopathy, intracranial calcifications, and cysts (LCC) is a very rare cerebral disorder, first described in 3 children in 1996. It has subsequently been reported in adults and children from Europe and America, but has not so far been reported from Asia. We report an adult patient with pathologically proven LCC from a tertiary care hospital in South India. He presented with features of ataxia and raised intracranial pressure. Magnetic resonance imaging of the brain showed multiple bilateral cerebral cystic lesions along with diffuse white matter lesions in the cerebral and cerebellar white matter, and computed tomography of brain showed multiple calcifications in the white matter and basal ganglia. A large right cerebellar cyst causing mass effect was surgically excised. Histopathologic features were consistent with earlier reports of LCC and showed Rosenthal fibers, angiomatous changes, and calcifications. Our report suggests that although it is rare, LCC has a global distribution.     

Multiple sclerosis with higher cerebral dysfunction: a case report

Higher cerebral dysfunctions such as aphasia, apraxia and agnosia have seldom been reported in multiple sclerosis (MS). 12 year-old right-handed boy felt unsteadiness of the body and headache for several days. Two months later, he had the same episode and complained of visual disturbance, and weakness and sensory disturbance on the face and the extremities. Additionally, he showed amnestic aphasia, acalculia, ideomotor apraxia, finger agnosia and right-left disorientation. Cerebrospinal fluid examinations revealed increases IgG, myelin basic protein and neuron specific enolase (11%, 25 ng/ml and 28.8 ng/ml, respectively). X-ray CT scan and MRI-CT examinations revealed sclerotic lesions on the left parietal white matter and the right mid-brain. The diagnosis was made as MS. He was treated with m-PSL (methyl-prednisolone) pulse therapy for three weeks and consecutively treated with PSL for four weeks. He recovered gradually, but visual disturbance and facial palsy remained. After seven months MRI-CT showed a high signal intensity on the left parietal white matter in spite of the disappearance of the lesion on X-ray CT scan. We suggest that these higher cerebral dysfunctions may result from the lesion of the left parietal white matter which produces a disconnection between each cortical area.     

Steroid-responsive diffuse cerebral white matter lesions in a case of intractable fungal meningoencephalitis]

We report a case of fungal meningoencephalitis with steroid-responsive diffuse cerebral white matter lesions. A 49-year-old male developed auditory hallucination, confusion and fever, on April, 1994. He was diagnosed as having cryptococcal meningoencephalitis based on the detection of cryptococcal antigens in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole resulted in improvement of his neurologic symptoms and CSF findings. For the next seven months, he was treated with oral fluconazole and the neurological status was stable. However, soon after the dose of fluconazole was tapered, he became confused and febrile, which made him admitted to our hospital. Neurological examination on admission showed disturbance of consciousness, disorientation and meningeal irritation. The CSF examination revealed mild pleocytosis (mostly lymphocytes), elevated protein and normal glucose levels, although fungus was not detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed spotty enhanced lesions in the periventricular white matters. The neurologic symptoms were once relieved after intravenous administration of fluconazole was started, but two months later, he became comatose and needed ventilatory support, despite amphotericine B therapy. Then, a needle brain biopsy targeting the white matter lesion was done. Histopathology of the specimen showed chronic inflammation with granuloma formation and T lymphycyte infiltrate around the small vessels, though fungus was not detected in the tissue. Combined therapy with corticosteroid and antifungal agents remarkably improved the neurological symptoms as well as the MRI findings. In the present case, fungal infection possibly induced an altered immune reactions which resulted in the steroid responsive diffuse cerebral white matter lesions.     

Cerebral white matter lacerations in children caused by repetitive head trauma

It has been known that infants less than 1 year develop cerebral white matter (WM) lacerations associated with head trauma, however, there has been no report of similar WM lesions over 1 year. We report three teenage boys (11, 12, and 18 years at final MRI studies) with acquired WM lacerations associated with recurrent head trauma who developed neurologic symptoms such as spastic paralysis, afebrile convulsions, and cognitive impairment. Two of them (patients 1 and 2) were given a diagnosis of autism spectrum disorder and had a history of repeated severe self-inflicted head trauma from preschool age. Patient 3, who practiced karate and boxing from preschool age, showed gradual declining intellectual ability. Brain MRI of the three patients revealed severe lacerations in the bilateral cerebral WM. Previous neuroimaging showed no WM lacerations at 4 and 5 years in patients 1 and 2, or mild WM lacerations at 17 years in patient 3, indicating the WM lacerations could have been acquired in childhood. It is suggested that repetition of head trauma in children can cause cerebral WM lacerations and brain dysfunction.     

Reversible White Matter Lesions During Ketogenic Diet Therapy in Glucose Transporter 1 Deficiency Syndrome

BackgroundGlucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport.PatientsWe describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene.ResultsWe initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet.ConclusionsThis is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome.     

Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats

There is evidence for chronic atrophy after human head trauma, which may be associated with long-term functional deficits. However, using established models of traumatic brain injury (TBI) only limited data are available for clarifying the extent of progressive gray and white matter atrophy. In the present study, male Sprague-Dawley rats underwent moderate (2.01-2.21 atm) parasagittal fluid percussion brain injury ( n=7) or sham ( n=3) surgery and were killed at 1 year post TBI. Semiserial sections were obtained through the neuraxis and double stained with hematoxylin and eosin to demarcate gray matter structures and Luxol fast blue for white matter visualization. Both ipsilateral and contralateral volume measurements were obtained for the following structures: cerebral cortex, hippocampus, dentate gyrus, thalamus, lateral ventricle, external capsule, internal capsule, cerebral peduncle and corpus callosum. Quantitative assessment of ipsilateral gray matter structures from TBI rats revealed significant reductions in cerebral cortical area measurements posterior from the trauma epicenter compared to sham animals. Importantly, several white matter tracts exhibited dramatic atrophy. A comparison of TBI and sham groups demonstrated a significant ( P<0.05) decrease in the external capsule and cerebral peduncle volumes ( P<0.007). In addition, there was a significant volume expansion (533% of control) of the ipsilateral lateral ventricle ( P<0.03). These novel data emphasize the need to clarify the pathophysiology of progressive white matter damage after TBI and the development of therapeutic strategies to target white matter pathology.     

A case of FK 506-induced leukoencephalopathy]

We reported a 15-year-old boy with an acute myelomonocytic leukemia and FK 506-induced leukoencephalopathy. He was received FK 506 for graft versus host disease occurred after peripheral blood stem cell transplantation. He, four weeks later, had generalized seizures and consciousness disturbance. The serum level of FK 506 was high (27.5 ng/ml). His brain MRI showed abnormal high intensity areas in the frontal and parietal white matter lesions on T2-weighted images. Neuropathological studies revealed the destruction of myelin sheeths and axons in the cerebral white matter corresponded with abnormal lesions on MRI. There were calcification and mineralization in the small vessel walls of the cortex and white matter. Osteopontin immunoreactivity was detected in the endothelial cells of small vessels. These findings suggest that the vascular damage was involved in the FK 506-induced leukoencephalopathy.     

Cerebral fat embolism: Pathologic changes in the brain after survival of 7 years

Summary A middle-aged man suffered severe injuries with multiple bone fractures when struck by a steel plate. The head was not traumatized. He showed the clinical picture of a cerebral fat embolism, followed by neurologic signs and mental deterioration over a period of 7 years. Extensive demyelination of the cerebral white matter was the dominant pathologic finding.We are indebted to Simon I. Miller, M.D., Denver, for his helpful cooperation and permission to study this case.     

Myelinopathia centralis diffusa (vanishing white matter disease) in a four-year-old boy

A four-year-old boy presented with moderate ataxia triggered by a minor head trauma several weeks ago. Discrepantly severe signal changes of cerebral white matter with almost CSF-isointense signal on all pulse sequences were detected at cranial MRI. Localized proton MR spectroscopy of cerebral white matter demonstrated an even decrease of all metabolites. Glycine was found elevated in CSF. This pattern of clinical history, MR imaging and spectroscopy features and elevated glycine in CSF is characteristic for a novel entity amongst the leukoencephalopathies of childhood. It was originally termed "myelinopathia centralis diffusa" and renamed "vanishing white matter disease" later.     

Computerized tomography of brain and optic nerve in multiple sclerosis: Observations in 100 patients,including serial studies in 16

Computerized tomography (CT) of the brain was carried out in 100 patients with established or suspected multiple sclerosis (MS). The optic nerves were also examined in 53 of these patients. Areas compatible with demyelinating lesions were found in the cerebral hemisphere white matter and less frequently in the brain stem in 47% of cases. The hemisphere lesions were commonly multiple, typically situated in the deep white matter and periventricular regions, and were often asymptomatic. Small areas with unduly low attenuation coefficients were found in one or both optic nerves in 52% of patients in whom the optic nerves were examined. While these areas may represent demyelinating lesions their significance remains uncertain in view of poor correlation with clinical and electrophysiological parameters of optic nerve damage. Cerebral cortical atrophy and/or ventricular dilatation was found in 44% of cases, the frequency and severity of atrophy increasing with age and duration of disease.Serial studies after intervals of up to 21 months were performed in 16 patients, providing the opportunity to study the natural history of the cerebral lesions. While in some cases no significant change occurred, in others white matter lesions underwent an increase, or a reduction in size, and in some cases new lesions appeared. In some patients minor degrees of atrophy became apparent over the period of the study.The value of CT in the investigation of patients with suspected MS and as a means of studying the natural history of the disease is discussed.     

Encephalopathy caused by visceral larva migrans due to Ascaris suum.

We described a patient with encephalopathy associated with visceral larva migrans (VLM) caused by Ascaris suum. He suffered from drowsiness, quadriparesis, eosinophilia and elevated serum IgE levels. Brain magnetic resonance (MR) imaging revealed multiple cerebral cortical and white matter lesions. Serological tests indicated recent infection with A. suum. Pulse steroid therapy relieved the patient's central nervous system symptoms and marked improvement of lesions on brain MR images. We concluded that the encephalopathy in this patient was probably caused by VLM due to Ascaris suum.     

Comparative Evaluation of the Cerebral and Cerebellar White Matter Development in Pediatric Age Group using Quantitative Diffusion Tensor Imaging

Age-dependent changes in the normal cerebral white matter have been reported; however, there is no study on normal cerebellar white matter maturation in developing brain using diffusion tensor imaging (DTI). We performed DTI in 21 children who had normal neurological assessment along with no evidence of any abnormality on imaging. The aim of this study was to compare the age-related changes in fractional anisotropy (FA) and mean diffusivity (MD) quantified from cerebral white matter (splenium and genu of the corpus callosum and posterior limb of the internal capsule) and cerebellar white matter (middle cerebellar peduncles, superior cerebellar peduncles, and inferior cerebellar peduncles) regions in healthy children ranging in age from birth to 132 months. Log-linear regression model showed best fit to describe the age-related changes in FA and MD both for cerebral and cerebellar white matter. In cerebral white matter, an initial sharp increase in FA was observed up to the age of 24 months followed by a gradual increase up to 132 months. In cerebellar white matter, sharp increase in FA was observed up to 36 months, which then followed a gradual increase. However, MD showed a sharp decrease in cerebral white matter up to 24 months followed by a more gradual decrease thereafter, while in cerebellar white matter after an initial decrease (6 months), it followed a stable pattern. This study provides normative database of brain white matter development from neonates to childhood. This quantitative information may be useful for assessing brain maturation in patients with developmental delay of the cerebral and cerebellar white matter.     

Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer's disease

Morphometric analysis of standardized gross cerebral slices from 16 patients with end-stage Alzheimer's disease (AD), 14 controls without neuropathological lesions or neurological disease, and 4 neurologically intact nondemented patients with histopathological lesions of AD was used to measure cross-sectional areas of cerebral cortex, white matter, subcortical nuclei, and the ventricular system. In AD, there was global cerebral atrophy of both cortex and white matter, selective atrophy of the amygdala and hippocampus, and ex vacuo hydrocephalus. In addition, in half the cases of AD, white matter atrophy was associated with overt histopathological evidence of patchy rarefaction of fibers and gliosis. Patients with preclinical AD had prominent and selective shrinkage of white matter comparable to that observed in AD, yet their cortical areas were normal. These observations suggest that white matter degeneration is an intrinsic component of AD. Moreover, its presence in preclinical AD where cortical atrophy is not evident indicates that cytoskeletal abnormalities associated with axonal degeneration may precede and perhaps cause the cortical atrophy observed in clinically manifested AD.     

White matter lesions and intra-arterial thrombolysis

The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT.     

MRI-pathological correlate of brain lesions in a necropsy case of HTLV-I associated myelopathy.

A postmortem case of HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis (TSP) with a history of remission and exacerbation of neurological signs and symptoms, resembling those of multiple sclerosis is reported. MRI analysis revealed lesions in the periventricular white matter in addition to atrophy of the thoracic spinal cord, characteristic of HAM/TSP. The cerebral periventricular areas consisted of ill-defined paucity of myelin sheaths with astrocytic gliosis and hyaline thickening of blood vessels. The poorly demarcated white matter lesions found in both brain and spinal cord were different from plaques found in multiple sclerosis. It is suggested that, in some cases of HAM/TSP, inflammatory lesions that destroy myelin can involve not only the spinal cord but also the cerebral periventricular white matter.     

脑皮质下小血管病变与脑萎缩的相关性分析

目的探讨脑皮质下小血管病变与脑萎缩的相关性。方法通过10例临床确诊为脑萎缩的病人的调查,收集其临床基本资料及头颅磁共振成像(magnetic resonance imaging,MRI)的结果及图像,评判其脑皮质下小血管的病变情况。结果所有病例颅脑MRI均发现显著的弥漫性脑白质病变(white matter lesions,WML)和多发的脑腔隙性梗死灶(lacunarinfarcts,LI)。结论颅脑MRI提示,脑皮质下小血管病变与脑萎缩共存,提供了其与脑萎缩可能有关的临床依据。     

A case of acute disseminated encephalomyelitis after renal transplantation]

We report a patient of acute disseminated encephalomyelitis (ADEM) in a recipient of renal transplantation. A 43-year-old man suffered from generalized convulsion and consciousness disturbance followed by coma on day 53 of after the transplantation. He was receiving several immunosuppressants, and an increase of serum antigen for cytomegalovirus was observed one day before the ictus. T2 and diffusion-weighted image of MRI showed high intensity lesions in the bilateral cerebral white matter, basal ganglia, thalamus, midbrain, pons and cerebellum. Examination of cerebrospinal fluid revealed elevated myelin basic protein level. The patient was diagnosed as having ADEM and was treated with methylpredonisolone pulse therapy in combination with intravenous immune globulin. He gradually recovered and became capable to eat and sit on a wheel chair. White matter lesions on MRI were also diminished. ADEM may occur in recipients of organ transplantation even if they have immunosuppressive treatment.     

Multiple sclerosis with extensive lesions, left hemiplegia, mental dysfunction and retrobulbar neuritis

Multiple sclerosis (MS) is usually diagnosed on the basis of the typical clinical course, with remission and exacerbation in multiple parts of the central nervous system (CNS). Recently, magnetic resonance imaging (MRI) has made a large contribution to the diagnosis of patients with MS. But it is difficult to make a definite diagnosis due to clinical variability of the disease and variable MRI findings. We report the case of a 26-year-old woman who developed progressive left hemiplegia, mental dysfunction, and had extensive bilateral cerebral white matter lesions diagnosed by brain MRI. Complete recovery from the left hemiplegia followed the use of corticosteroid, and her brain MRI findings also improved after medication. Early in the clinical course it was difficult to differentiate between multiple sclerosis and granulomatous angiitis of the CNS. After recovery from the first episode of left hemiplegia and mental dysfunction, she developed acute visual disturbance five months after her first admission. Readmission followed and her retrobulbar neuritis was successfully treated by methylpredonisolone pulse therapy. In summary, she experienced two episodes of neurological deficit, had left hemiplegia and mental dysfunction associated with multiple lesions in bilateral cerebral white matter in brain MRI, and the left retrobulbar neuritis with delay of P100 by visual evoked potential study. Due to these two episodes we concluded that she had multiple sclerosis. Though the initial diagnosis was difficult, prompt treatment and close follow-up was important, since multiple sclerosis and granulomatous angiitis of the CNS can both recur.