Focal Cortical Atrophy Research Articles

Cases from the greater Boston epilepsy society.

The Greater Boston Epilepsy Society (GBES) is an informal group consisting of academic physicians, private practice neurologists, researchers, neuropsychologists, neuropsychiatrists, social workers, nurses, and other professionals devoted to the care of patients with epilepsy. It was founded in 1995 by Dr. Andrew Cole from the Massachusetts General Hospital and Dr. Gregory Holmes, at the time from the Children's Hospital of Boston, with the goal of providing an informal educational forum and, perhaps more importantly, an opportunity to meet and establish camaraderie with other local epilepsy professionals. Three times a year, the members gather for dinner and an educational event. The first of these meetings, entitled “Great Cases in Epilepsy”, has been devoted to the discussion of clinical cases, typically presented in a case format by the clinical epilepsy fellows at a local teaching hospital. The Boston area, being blessed with a large concentration of independent epilepsy centers, provides a unique collective of clinical and research resources and as such draws a rich assortment of interesting or unusual cases of epilepsy. The case presentation forum accomplishes two objectives. Firstly, it provides a means for epileptologists, particularly residents and clinical fellows, to learn about cases in epilepsy that are sufficiently unusual that they might not be countered during their training but are of such importance that they should be recognized during the one or few times they may encounter them in their careers. Secondly, for a particularly vexing case, the collective wisdom of the group may often provide further insights into the diagnosis and management of the patient in question. We present this year's case presentations in this issue of Epilepsy & Behavior Case Reports. Dr. Marcus Ng uses the Creutzfeldt–Jakob Disease as a model to examine a rational approach toward the treatment of nonconvulsive seizures. Dr. Sandipan Pati presents an unusual patient with epilepsy and progressive focal cortical atrophy. Dr. Ammar Kheder presents an unusual case of burst suppression pattern on EEG that is a physiological, rather than pathological, phenomenon. Dr. Stephen VanHaerents describes a case of anti-NMDAR encephalitis with the newly described “extreme delta brush” pattern and provides what we believe is the first report of its persistence. Dr. Swapna Putta presents the clinical, electrographic, and radiological findings of an unusual case of occipital lobe seizures in a patient with diabetic nonketotic hyperglycemia. Dr. Matthew Rose's case on neuroschistosomiasis reminds us that the mundane first seizure presentation may be a result of a most unusual etiology (at least in Boston).

Renal Involvement in Antiphospholipid Syndrome

Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

Evolution of MRI changes in Rasmussen's encephalitis

We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.

PICK ‘N’ MIX: NEUROPATHOLOGICAL DETECTION OF PERI–TUMOUR TAUOPATHY

BackgroundRadiotherapy is used to treat recurrent oligodendrogliomas, WHO grade 2 tumours. Potential morbitities include steroid–responsive radiation necrosis and radiation leucoencephalopathy, characterised pathologically by reactive astrogliosis, focal necrosis, demyelination, axonal loss,...

Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: A DT MRI study and a literature review

Nonfluent (NFV) and semantic (SV) variants of primary progressive aphasia (PPA) are associated with distinct patterns of focal cortical atrophy and underlying pathology. Previous diffusion tensor (DT) MRI studies showed a more ventral white matter (WM) involvement in SV patients and a more widespread frontal involvement in NFV. Aim of this manuscript is twofold. First, we wished to provide a brief state-of-the-art review on WM damage in PPA. Second, we used DT MRI to assess the topography of WM microstructural damage along dorsal and ventral language pathways and corpus callosum in patients with NFV and SV. Our findings show that the two PPA variants share an overlapping pattern of dorsal and ventral pathway abnormalities. In addition to these common abnormalities, variant-specific WM changes were also found, with NFV patients having a more severe damage to the dorsal (fronto-parietal) WM connections within the left superior longitudinal fasciculus/arcuate and SV patients showing a greater left ventral tract involvement (inferior longitudinal and uncinate fasciculi). These findings offer evidence that both dorsal and ventral language networks may contribute to the relatively selective deficits in NFV and SV patients.

Catastrophic antiphospholipid syndrome presenting with sudden renal failure: The lesson lies in vascular lesions.

Catastrophic antiphospholipid syndrome presenting with sudden renal failure: The lesson lies in vascular lesions.

Is progressive upper-body apraxia a corticobasal syndrome?

Corticobasal degeneration (CBD) is characterized by various clinical manifestations including corticobasal syndrome, progressive supranuclear palsy-like syndrome and frontotemporal dementia. Focal cortical atrophy syndrome as the initial manifestation rarely occurs in CBD. Here, we present a 62-year-old man and a 70-year-old man who were admitted due to clumsiness in the arms. On initial neurological examination, they showed asymmetric limb apraxia without parkinsonism or global cognitive dysfunction. Brain MRI showed focal atrophy in the frontal and prefrontal cortices, and brain positron emission tomography scan revealed decreased metabolism in these same brain locations. Although these patients developed parkinsonism and dystonia within several years, the neurological signs were limited to the arms for a long period. “Progressive upper-body apraxia” may be a rare clinical manifestation of CBD which shows a benign clinical outcome. The patients described may enhance our understanding of the clinical heterogeneity of this disease.

Beneficial Effects of Fluvoxamine for Chorea in a Patient With Huntington’s Disease

Beneficial Effects of Fluvoxamine for Chorea in a Patient With Huntington’s Disease

Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis

Objectives This study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN).Methods We studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy.Results Elevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage.Conclusions Our study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.

Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis

ObjectivesThis study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN).MethodsWe studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy.ResultsElevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage.ConclusionsOur study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.

Dual Pathology in Rasmussen’s Encephalitis: A Report of Coexistent Focal Cortical Dysplasia and Review of the Literature

Rasmussen's encephalitis is a well-established, albeit rare cause of medically intractable epilepsy. In a small number of Rasmussen's cases, a second pathology is identified, which independently can cause medically intractable seizures (dual pathology). This paper documents a case of a 13-year-old male who presented with medically intractable epilepsy. The patient underwent a series of surgical resections, early on resulting in a diagnosis of focal cortical dysplasia and later yielding a diagnosis of coexistent Rasmussen's encephalitis, marked by chronic inflammation, microglial nodules, and focal cortical atrophy, combined with focal cortical dysplasia (Palmini et al. type IIA, ILAE type IIA). The literature on dual pathology in the setting of Rasmussen's encephalitis is reviewed.

Uniplanar Nystagmus Associated with Perceptual and Cognitive Visual Dysfunction due to Presumed Focal Ischemic Occipital Cortical Atrophy: A Missed Diagnosis and New Observation

Uniplanar nystagmus has been described in relation to pathology of the brain stem, retina, optic nerve, sensory visual deprivation, periventricular leucomalacia, and drug toxicity. This paper describes a case of uniplanar nystagmus associated with features of higher visual dysfunction and a presumed focal insult to the occipital lobes following an episode of neonatal apnea.

Nephropathy associated with antiphospholipid antibodies in patients with systemic lupus erythematosus

Nephropathy associated with antiphospholipid antibodies (aPL) has been proposed as a risk factor of worse renal prognosis in patients with systemic lupus erythematosus (SLE). The purpose of the current study was to evaluate the prevalence of aPL-associated nephropathy (aPLN) among patients with lupus nephritis and to describe their functional renal outcome. A total of 79 renal biopsies from 77 patients followed at the Hospital Clinic, Spain were analysed. Each renal biopsy was evaluated by a pathologist who was blinded to the aPL status. Thrombotic microangiopathy (TMA), fibrous intimal hyperplasia (FIH), fibrocellular arterial occlusion (FAO), focal cortical atrophy (FCA), and tubular thyroidization as lesions suggestive of aPLN were identified. aPLN was found in nine (11.4%) biopsies. TMA was found in three (33.3%) cases whereas chronic aPLN, represented by FIH and FCA, was found in four (44.4%) and three (33.3%) cases, respectively. A significant association between the presence of aPL and aPLN was found (p = 0.003). Patients with lupus anticoagulant (LA) plus IgG anticardiolipin antibodies (aCL) showed an increased prevalence of aPLN (OR: 3.61, 95% CI 1.28-5.14; p = 0.002). Creatinine levels were significantly increased in patients with aPLN compared with those with aPL without aPLN (p = 0.038). However, no significant difference in complete remission, partial remission, not response, and established renal damage between groups was observed at the end of follow-up. The aPL have an important role in the pathogenesis of renal lesions in SLE patients. Prospective studies are needed to address the role of aPLN in the long-term outcome of SLE patients with positive aPL.

Focal cortical and subcortical atrophy in early Parkinson's disease

Neurodegeneration in clinically manifest Parkinson's disease affects the substantia nigra pars compacta, and gradually spreads to the limbic cortices and the neocortex. We used MRI imaging coupled with automated surface reconstruction and segmentation methods to examine cortical thickness and subcortical volumes in nondemented, early-stage Parkinson's disease patients compared to matched healthy control participants. These methods, which have been previously used to document cortical thickness changes in patients with Alzheimer's disease and Huntington's disease but not Parkinson's disease, use MR signal intensity information and the geometric constraints of the cortical and subcortical structures for an accurate tissue classification. Parkinson's disease patients were matched to the control group in psychomotor processing speed and executive functioning, but showed higher anxiety state scores. Our results demonstrated focal cortical thinning in the Parkinson's disease group in the orbitofrontal cortex, ventrolateral prefrontal cortex, and occipito-parietal areas. Subcortically, striatal volume loss was noted. These results demonstrate that both cortical and subcortical structural changes occur at relatively early stages of the disease, and are discussed in terms of the emotional dysregulation that occurs early on in patients with Parkinson's disease.

Neuroimaging findings in children with retinopathy-confirmed cerebral malaria

Purpose To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria. Materials and methods In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists. Results Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9–84 months old), 15 had adverse neurologic outcomes—11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7–18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11). Conclusions The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease.

Extent of cerebellum, subcortical and cortical atrophy in patients with MS: A case-control study

Cortical and subcortical atrophy occurs in multiple sclerosis (MS) and relates to clinical outcomes. FreeSurfer, a voxel-based automated software for brain reconstruction was used to investigate the extent of subcortical and cortical atrophy in 71 MS and 17 clinically isolated syndrome (CIS) patients, and 38 normal controls (NC), and to relate group differences to disease type and severity. Segmentation was performed on 3D SPGR T1-weighted MRI 1.5T images. Region-specific subcortical tissue volumes were calculated in mm 3 and cortical thickness in mm. Logistic regression and general linear model analyses, adjusted for age and intracranial volume, examined differences between NC, MS and CIS patients and disease subtypes. The MS group was characterized by significantly lower volumes of thalamus (left and right p < 0.0001), left inferior lateral ventricle, third ventricle ( p < 0.0001), ventral diencephalon, pallidum and putamen bilaterally, as well as of right accumbens and brainstem with corresponding bilateral increase in volumes of lateral ventricles ( p < 0.01). Focal cortical atrophy areas in the thalamus, inferior parietal lobule of left hemisphere and in right precuneus were also significant in the MS sample. Versus CIS patients, RR or progressive MS patients showed significantly lower volumes of subcortical regions and cortical thinning. Hippocampal atrophy appeared only in advanced disease stages. Cerebellum WM volumes were significantly lower in MS and CIS patients vs. NC. Subcortical and cortical atrophy correlated with higher disability as measured by EDSS. This study confirmed selective deep gray matter atrophy (mostly thalamic), revealed cerebellum WM atrophy from the earliest clinical stages, and showed that cortical thinning advances with disease progression.

L’amnésie pure progressive : un syndrome amnésique avec préservation de l’autonomie

Introduction Pure progressive amnesia, a form of progressive focal cortical atrophy is thought to represent the early stages of a rare form of Alzheimer's disease (AD). This syndrome is characterized by the insidious and slowly progressive breakdown of memory, in the absence of a significant impairment in other cognitive domains or in the realm of behavior. The aims of the present study were to contribute to the characterization of this poorly documented type of amnesia, to compare it with other forms of amnestic syndromes resulting from lesions to the medial temporal lobes and to discuss its potential pathophysiological basis. Patients and method We carried out three single case studies in patients presenting with pure progressive amnesia. They all underwent a neuropsychological evaluation that included an extensive assessment of spatial and recognition memory, along with brain magnetic resonance imaging and a cerebral blood flow study. Results All three patients had a severe deficit in the storage of context-free information, along with a severe visual recognition memory impairment, as previously reported in a case study on a patient with pure progressive amnesia (Cognitive Neuropsychology 23 (2006) 1230–1247). Yet, spatial memory remained well preserved, and patients maintained totally independent in everyday life. In addition, a significant atrophy of the medial temporal structures was found. Discussion This specific pattern of impairment differs from other types of amnestic syndromes after medial temporal damage and raises the question of lesional topography, as well as possible compensatory phenomena. We suggest that pure progressive amnesia results from selective damage to the ventral subhippocampal route into the hippocampal formation leading to impaired context-free memory. Spatial memory may remain intact because the dorsal parahippocampal route into the hippocampus remains functional. Pure progressive amnesia may contribute to a better understanding of the neural systems involved in declarative memory and provide a better understanding into the nature of the memory impairment that characterizes the initial stages of AD.

Renal Involvement in the Antiphospholipid Syndrome (APS)—APS Nephropathy

Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

Anarthrie progressive : une entité propre

Introduction First described 15 years ago, primary progressive anarthria is a focal cortical atrophy defined as a rare progressive impairment of speech associated with orofacial apraxia and leading to mutism with a frontal lobe syndrome. The aim of this study was to analyze clinical and neuropsychological data and results of complementary tests in a series of patients presented with primary progressive anarthria. Material and methods We, retrospectively, studied five patients with primary progressive anarthria. We particularly analyzed the following parameters: age at onset, age at the diagnostic, disease time from onset to first consultation, the initial orientation, the neuropsychological and clinical data at the first visit, electromyography, brain MRI, and single photon emission computed tomography (SPECT) findings. Clinical and neuropsychological data were used to monitor disease course. Results The mean age at onset of symptoms was 75.2 ± 5.8 years. Patients were primarily referred to a specialist in memory disease ( n = 3) or a specialist in motor neuron disease ( n = 2). The time from onset to first consultation was 11.2 ± 3 months. Anarthria was associated with dysexecutive syndrome and sometimes, with impaired comprehension. Electromyography was always normal. Cranial MRI showed temporal or left frontal atrophy ( n = 3). Spect revealed decreased cerebral blood flow predominating in the left frontal or temporal region ( n = 4). Conclusion Long delay for specialist consultation and inadequate initial orientation retard disease diagnosis, leading to severe incapacity. Complementary studies are required to confirm diagnostic and to rule out lateral amyotrophic sclerosis. During the early stages, involvement of the premotor cortex may be considered due to the speech apraxia. Secondary motor orofacial disturbances suggest an extension to the motor cortex. Primary progressive anarthria is a distinct individual entity within the spectrum of focal cortical atrophies.

Treatment for Anomia in Semantic Dementia

Anomia is a striking and consistent clinical feature of semantic dementia (SD), a progressive aphasia syndrome associated with focal cortical atrophy of the anterior temporal lobes. Word retrieval deficits in patients with SD have been attributed to the loss of conceptual knowledge, resulting in an impairment referred to as semantic anomia. Whereas an abundance of research has been dedicated to treatment for anomia in individuals with focal brain damage due to stroke, considerably less work has been done regarding treatment for patients with progressive language decline. The purpose of this article is to review the available literature concerning the nature and treatment of anomia in individuals with SD. Several studies have shown that new lexical learning remains possible in these patients. However, newly learned information is likely to be constrained by the learning context, and increased reliance on perceptual and autobiographical contextual information may be necessary to provide critical support for new vocabulary acquisition. There is also evidence suggesting that treatment may slow the progression of anomia over time, even affording some protective benefit to lexical items that are not yet lost. However, treatment efforts are likely to be most beneficial at early stages of the disease, when residual semantic knowledge as well as relatively spared episodic memory may support new learning.