Mild Cortical Atrophy Research Articles

Nicergoline augmentation treatment of late onset depression

AbstractBackground: Elderly patients with depression have more ischemic lesions on magnetic resonance imaging (MRI) of the brain than those without depression. Therefore, late onset depression might be associated with neurobiological etiology, especially vascular lesions of the brain. Recently nicergoline, which is an ergoline derivative and increases cerebral blood flow, has been reported to be effective for vascular depression. However, it remains unclear whether late onset depression without ischemic lesions or vascular risk factors can be improved by this compound.Methods: The present study reports the case of a 69‐year‐old woman with depression, which consisted of mild depressive mood, severe loss of drive and appetite, and moderate cognitive impairment that developed over 8 months. Treatment with 150 mg of sulpiride, 40 mg of paroxetine hydrochloride, and 0.5 mg of etizolam everyday for 5 months had no effect on the patient. MRI of the brain showed mild cortical atrophy in the bilateral frontal and parietal lobes with no remarkable ischemic lesions. A mild decrease of relative cerebral blood flow (CBF) in the atrophic regions was shown by 99mTc‐HMPAO single photon emission computed tomography (SPECT). After sulpiride treatment was discontinued, the patient took 15 mg of nicergoline daily in addition to selective serotonin reuptake inhibitor (SSRI) treatment.Results: The patient's symptoms were improved after 2 weeks and 99mTc‐HMPAO SPECT of the brain showed a slight improvement of relatively decreased CBF in the regions.Conclusion: Nicergoline might have a therapeutic potential as an augmentation strategy for late onset depression.

Neurologic evaluation of workers previously diagnosed with solvent-induced toxic encephalopathy.

We examined 52 railroad workers with long-term occupational solvent exposures (average 22 years duration) who had been previously diagnosed by others as having solvent-induced toxic encephalopathy. All described episodes of transient intoxication associated with occupational solvent exposure. Persistent symptoms developed, an average, 16 years after exposure onset and included impaired memory (38), altered mood (21), imbalance (18), and headache (17). Thirteen workers had mild mental status abnormalities, but none fulfilled conventional clinical criteria for encephalopathy or dementia. None had abnormal blink reflex (51) or abnormal electroencephalographic (39) studies. Eight of 47 magnetic resonance imaging studies showed evidence of scattered ischemic lesions among workers with known diabetes mellitus (2), elevated blood pressure (4), or peripheral vascular disease (2). One magnetic resonance imaging scan showed mild cortical atrophy. In stepwise multiple linear and logistic regression models, no statistically significant (P < 0.05) dose-response relationships were found between exposure duration and symptoms or signs that were suggestive of encephalopathy. However, the number of symptoms (P < 0.001) and the number of signs (P = 0.05) were associated with current use of central nervous system-active medications. Further, lower Mini-Mental Status Examination scores were associated with a history of alcohol abuse (P = 0.01) and lower educational level (P = 0.03). The number of chief symptoms involving memory, mood, balance, or headache differed significantly among workers in different geographic sites (F(3.48) = 2.94, P = 0.04), a finding that was not explained by job title or exposure duration. There also was a significant (P = 0.0001) inverse relationship between initial exposure year (r2 = 0.60) or total years of exposure through 1987 (r2 = 0.56) and interval to major neurologic symptom onset, suggesting that factors other than solvent exposure account in part for worker complaints. We found no objective neurologic evidence supportive of toxic encephalopathy or any other uniform syndrome among these individuals, and most complaints were explained by neuropsychological factors or conditions unrelated to occupational solvent exposure.

Neuroimaging findings of four patients with Sandhoff disease

Sandhoff disease is a severe form of GM 2 gangliosidosis that is caused by the deficiency of both hexosaminidase A and B. Startle reaction, hypotonia, psychomotor retardation, and blindness are the main clinical features. Presented are computed tomography and magnetic resonance imaging findings of four patients with Sandhoff disease diagnosed by enzymatic analyses. Bilateral homogeneous thalamic hyperdensity was evident on computed tomography. Magnetic resonance imaging scans revealed mild cortical atrophy, a thin corpus callosum, and abnormal signal intensities in the caudate nucleus, globus pallidum, putamen, cerebellum, and brainstem. No correlation was evident between the severity of the central nervous system imaging findings and the clinical pictures. In this article the neuroimaging findings of four patients with Sandhoff disease are discussed.

Fucosidosis: immunological studies and chronological neuroradiological changes

A 3.5‐y‐old boy of Arabic origin had the clinical features of both type 1 and type 2 fucosidosis, consistent with an intermediate form of the disease. The activity of his leucocyte alpha L‐fucosidase was absent. He presented with recurrent sinopulmonary infection and otitis media in addition to paronychia and a periapical dental abscess. Investigation of his systemic immune function did not reveal a significant underlying defect, but subtle abnormalities, particularly of antibody production and secretory IgA, cannot be excluded. The cranial magnetic resonance images showed periventricular and subcortical white matter abnormalities and mild cortical atrophy in addition to globus pallidus changes.

Reversible cortical atrophy and cognitive decline induced by valproic acid

An 18-year-old male suffered from familial progressive myoclonic epilepsy from the age of 7 years. In addition to seizures, there was a marked decline in school performance. At the age of 14 years, sodium valproate was started as add-on therapy; 2 weeks later he was hospitalized in a stuporous state. The serum level of valproate was within the therapeutic range. Cognitive evaluation disclosed moderate mental retardation. No metabolic abnormalities were detected. Valproate was discontinued and during the 4 following months, a slow but significant improvement was documented in cognitive functions. Repeated assessment was within the range of mild mental retardation. Initially, magnetic resonance imaging (MRI) showed mild cortical atrophy. A subsequent MRI study performed 2 years later was normal.

Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil.

[123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected as regions of interest to estimate receptor binding 5 days to 23 months after the stroke. A two-compartment model was used to compute the distribution volume (Vd) of iomazenil in relative units, with Vd proportional to benzodiazepine receptor concentration. The side-to-side asymmetry ratio of Vd was calculated. The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted cortex showed significant decrease of Vd (P < .001). Contralateral cerebellum showing diaschisis had no reduction of Vd. On MRI, obtained 3 or 6 months after the stroke, mild cortical atrophy was observed in two reperfused areas where the asymmetry ratio was moderately reduced (0.64 and 0.80). The reduction of benzodiazepine receptor concentration in reperfused cortex that remained structurally intact is likely to be the result of injury involving only a limited number of neurons (ie, incomplete infarction). Our data suggest that the degree of viability of ischemic cortex apparently salvaged by early reperfusion can be quantified by iomazenil.

Slowly progressive impairment of spatial exploration and visual perception

Abstract We describe three cases of progressive visuo-spatial impairment. When tested, all patients exhibited Balint-Holmes' syndrome. Functions of other cognitive domains, including memory, were initially preserved. CT, MRI and PET scans revealed mild cortical atrophy, in one case more pronounced in the posterior part of both parietal lobes. The patients were followed up for several years and the progressive cognitive impairment extended to other cognitive functions (language, memory and executive functions), becoming indistinguishable from the typical profile of Alzheimer's disease (AD). However, the selective impairment of visuo-spatial functions at onset, and the extensive period for which these disorders remained isolated, leave their diagnostic characterization open to debate.

The neuropathologic diagnostic criteria of frontal lobe dementia revisited. A study of ten consecutive cases.

Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of: dementia and prominent symptoms and signs of the frontal type; a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions. We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type: 1. If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease. 2. If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II-III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers. 3. When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.

Chronic carbon disulfide encephalopathy.

To understand central nervous damage after long-term exposure to carbon disulfide (CS2), 10 patients who had polyneuropathy with various neuropsychiatric symptoms in a viscose rayon plant were studied. Clinical and laboratory examinations including electroencephalography (EEG), brain computed tomography (CT), brain magnetic resonance images (MRI), and carotid duplex sonography were carried out. Clinically, headache, unpleasant dreams, memory impairment, fatigue, anorexia and emotional lability were common in these patients while 2 patients had stroke episodes. EEGs were all normal. Brain CT scan showed mild cortical atrophy in 3 and low density lesions in the basal ganglia in 3. Brain MRI studies also disclosed mild cortical atrophy in 4 and multiple lesions involving the basal ganglia and corona radiata in 4. Carotid duplex sonography revealed mild atherosclerosis with plaques (< 20% stenosis) of extracranial vessels in 6. However there was no significant difference in flow velocities and flow volumes in the extracranial carotid arteries between patients and the normal controls. Interestingly, 2 patients had multiple brain lesions in the subcortical white matter but without strokes. In conclusion, encephalopathy with possible strokes may occur after chronic exposure to CS2, as well as polyneuropathy. The lesions usually involve the basal ganglia and subcortical white matter. Furthermore, MRI study may detect brain lesions particularly in the subcortical white matter areas before the occurrence of stroke.

Are Himalayan Sherpas Better Protected against Brain Damage Associated with Extreme Altitude Climbs?

1. The potential risk of brain damage when low-landers attempt to climb the highest summits is a well-known fact. However, very little is known about what occurs to Himalayan natives, perfectly adapted to high altitude, when performing the same type of activity. 2. Taking into account their long-life climbing experience at extreme altitudes, we examined seven of the most recognized Sherpas with the aim of performing a comprehensive neurological evaluation based on medical history, physical examination and magnetic resonance brain imaging. We compared them with one group of 21 lowland elite climbers who had ascended to altitudes of over 8000 m, and another control group of 21 healthy individuals who had never been exposed to high altitude. 3. While all of the lowland climbers presented psychoneurological symptoms during or after the expeditions, and 13 of them (61%) showed magnetic resonance abnormalities (signs of mild cortical atrophy and/or periventricular high-intensity signal areas in the white matter), only one Sherpa (14%) showed similar changes in the scans, presenting neurological symptoms at extreme altitude. The neurological examination was normal in all three groups, and no neuroimaging abnormalities were detected in the control group. 4. The significant differences, in both clinical and neuroimaging terms, suggest that Sherpa highlanders have better brain protection when exposed to extreme altitude. Although the key to protection against cerebral hypoxia cannot be established, it is possible that an increase in the usually short period of acclimatization could minimize brain damage in those low-landers who attempt the highest summits without supplementary oxygen.

Neonatal-onset propionic acidemia: Neurologic and developmental profiles, and implications for management

Objectives: To document the clinical and neurodevelopmental profiles of a cohort of patients with neonatal-onset propionic acidemia and to determine the efficacy of current therapy with respect to outcome. Method: The clinical, neurologic, and developmental status of six patients was prospectively evaluated during a 15-month period. Previous clinical and biochemical data were ascertained from hospital records to determine longitudinal nutritional status, number of episodes of hyperammonemia with ketoacidosis, and developmental performance with respect to age. Results: No deaths resulted from propionic acidemia since the identification of the oldest patient in the series in 1980. Therapeutic intervention (e.g., gastrostomy tube feeding) resulted in improved nutritional status and possibly contributed to improved survival. All children had hypotonia, resulting in a significant effect on motor development; however, focal neurologic deficits and evidence of movement or seizure disorder were absent. Mild cortical atrophy was evident on cranial magnetic resonance imaging in four patients. All children, including two patients with no significant episodes of hyperammonemia and normal growth since the neonatal period, had a mild to moderate degree of intellectual impairment. Conclusions: The results of our study suggest that current therapy for neonatal-onset propionic acidemia is associated with improved survival and nutritional status, and an absence of focal neurologic deficits. However, hypotonia and cognitive delay were still present, even in children with “optimal” metabolic control. Additional therapeutic advances are required to improve the developmental and cognitive outcome. (J PEDIATR 1995;126:916-22)

SEIZURES: III

A 60‐year‐old African‐American man was admitted to the hospital in October 1991 with seizures and right hemiparesis. He had end‐stage renal disease (ESRD), presumed due to hypertension and/or analgesic nephropathy, and had been on maintenance hemodialysis since July 1987. Noncontrast CAT of the brain revealed mild cortical atrophy and non‐specific while matter ischemic changes. Contrast CAT showed a right hemisphere CVA, and magnetic resonance imaging (MRI) suggested a right frontal meningioma. Cerebral arteriogram was confirmatory, and he underwent resection of the fronto‐parietal tumor in early November 1991. Past medical history included over 20 years of hypertension, angina for five years, gout, and peptic ulcer disease. Cardiovascular evaluation of exertional dyspnea and bilateral calf weakness included a negative thallium stress test and minimal to moderate flow impairment of tibial‐peroneal vessels by Doppler. Low iron stores led to upper and lower endoscopy and a colonic polypectomy. There was a question of an allergic reaction to intravenous iron administration (the patient reported lip swelling), and erythropoietin therapy was started in December 1990 (starting hematocrit was 23%). Hemodialysis access was achieved via a Brescia‐Cimino arteriovenous fistula in his left arm, which developed extensive upper arm and shoulder collaterals, leading to a fistulogram and a diagnosis of subclavian stenosis in January 1989. Angioplasty was successful, and repeat fistulogram was unremarkable in February 1991. Blood pressure control was usually adequate, ranging from 140–180/80–100 on diltiazem, clonidine, and captopril. Occasional elevation to 210/120 were seen. In the months prior to the seizure, his treatments were adjusted because of low Kt/V (by increased dialyzer surface area and increased time). Hematocrit had risen to 30%‐33% with erythropoietin therapy (2000 Units thrice weekly). Hemodialysis was accomplished without heparin use, due to his gastrointestinal bleeding history. He was felt to be gaining “flesh” weight. In late March 1992, he had a tonic‐clonic seizure. Repeat CAT scan of the brain was unchanged. He was started on phenytoin thrice daily, but he discontinued therapy and had two more seizures (with negligible serum levels of phenytoin) in April 1992. In May, he was readmitted after another tonic‐clonic seizure. Phenytoin levels were in the therapeutic range, and CAT scan was again unchanged. Phenobarbital was added to his regimen. Drowsiness limited his compliance, and he had several additional seizures. In late July, he suffered a respiratory arrest shortly after a seizure.

Presentation and course of AIDS dementia complex

To assess the clinical presentation and course of the AIDS dementia complex (ADC). Retrospective study of a consecutive series of symptomatic HIV-1-infected patients [Centers for Disease Control and Prevention (CDC) stages IVA, B, C and D] evaluated for neurological symptoms between 1982 and 1992. An academic referral centre for AIDS. A total of 536 symptomatic HIV-1-infected patients evaluated for neurological symptoms between 1982 and 1992. Zidovudine treatment, which was introduced in The Netherlands on 1 May 1987 for patients with severe symptoms of HIV infection (CDC stages IVA, B, C and D). Diagnosis of ADC and CD4 cell count, clinical features, neuropsychological abnormalities, computed tomography (CT) and magnetic resonance imaging (MRI) abnormalities, cerebrospinal fluid (CSF) findings and course in patients with ADC. ADC was diagnosed in 40 out of 536 (7.5%) immunosuppressed, neurologically symptomatic HIV-1-infected patients in CDC stage IV, and was the AIDS-defining illness in six. The mean CD4 cell count of the 40 patients with ADC was 109 x 10(6)/l. Neuropsychological abnormalities in 15 out of 17 patients tested were in accordance with subcortical dementia. On CT scan of the brain, 70% showed no or only mild cortical atrophy. MRI was more sensitive than CT scan for detecting white matter abnormalities (73 versus 35%; P = 0.02). CSF examination showed mononuclear pleocytosis in 25%, protein level increase in 55%, and HIV-1 p24 core protein in 38% (13 out of 34). The mean survival was 6.7 months in the 40 ADC patients, but 4 months in 20 patients who had never used zidovudine, compared with 14.8 months in 10 patients who started zidovudine after they were classified as having ADC (P < 0.001). Three of these 10 patients improved remarkably, and two slightly, after starting zidovudine. ADC developed after discontinuation of zidovudine in nine patients. Only one patient developed ADC while receiving 600 mg zidovudine. MRI is more sensitive than CT for detecting white matter abnormalities. To date, there is no specific or sensitive CSF marker for ADC. Zidovudine may improve symptoms and prolong survival in patients with ADC, which rarely developed with continued zidovudine use in our study.

Magnetic Resonance Imaging (MRI), Neurobehavioral Testing, and Toxic Encephalopathy: Two Cases

The objective of this investigation was to examine cerebral magnetic resonance imaging (MRI) pathology and functional deficits demonstrated by neuropsychological testing in cases of toxic encephalopathy. Two subjects, occupationally exposed to toxic chemicals, were studied. As part of their neurological assessment, MRI was done and each underwent a neuropsychological battery for patients with toxic exposures (White et al. Clin. Neuropharmacol. 13(5), 392–412, 1990). In Case 1, who was exposed to inorganic mercury, MRI showed mild central and cortical atrophy. Punctiform foci (T2) were noted in both frontal regions underlying the precentral gyri and in the subcortical myelin. Neuropsychological testing showed problems in cognitive flexibility, cognitive tracking, inhibiting perseveration, fine manual motor coordination, visuospatial analysis and organization, memory, and affect and personality. In Case 2, who was exposed to 2,6-dimethyl-4-heptanone, MRI showed multiple small foci in the white matter and pons. Neuropsychological testing indicated affective changes, deficits in manual motor speed, verbal fluency, visuospatial organization, and short-term memory. Lack of aphasia in patients with toxic encephalopathy indicates that neurotoxins probably affect subcortical and mesial temporal structures more than cortical gray matter. These MRI studies show subcortical sites of pathology.

Primary progressive freezing gait.

Freezing gait is an incapacitating symptom often observed in patients with Parkinson's disease. It has been less frequently described in association with multi-infarct state, multisystem atrophies, and normotensive hydrocephalus. In our movement disorder clinic, we have diagnosed (and followed up to 3 years; median, 16 months), 18 patients in whom progressive freezing gait was the sole neurological dysfunction. These 15 men and 3 women (aged 60-82 years; 74 +/- 6) were subjected to an extensive neurological workup that included clinical evaluation, videotaping for grading of gait disability, comprehensive blood and cerebrospinal fluid (CSF) analysis, and brain computed tomography (CT) and magnetic resonance imaging (MRI). Mean disease duration was 2.5 +/- 1.9 years (range, 0.5-6). Neurological examination disclosed freezing gait, often associated with varying degrees of postural instability. The degree of freezing gait ranged from sudden motor blocks only when confronted with obstacles to severe disability with total inability to start walking requiring a walker, massive assistance, or a wheelchair. However, patients could mimic gait movements with absolutely no freezing when seated or lying prone, and most of them could overcome arrests by the "walking-over-lines" maneuver. Otherwise, neurological examination was normal with no signs of bradykinesia, rigidity, or tremor. Blood chemistry and CSF analysis were normal. Brain CT and MRI were normal or showed mild cortical atrophy in 12 and putative lacunes in 6 patients. Therapy with levodopa or dopamine agonists was ineffective. During the follow-up period, a gradual progression of the freezing gait was observed. However, it remained unaccompanied by any other neurological findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial MR imaging in Creutzfeldt-Jakob disease

Serial magnetic resonance (MR) imagings of two autopsied patients with Creutzfeldt-Jakob disease (CJD) are presented. Both patients showed a dramatic progression of brain atrophy. The initial MR imagings were, however, interpreted as normal except for localized mild cortical atrophy in one patient. When a normal MR image is obtained in a demented middle-aged or aged patient, CJD may still need to be ruled out: follow up MR imaging may be useful.

EXPRESSIVE DYSPHASIA POSSIBLY RELATED TO FK506 IN TWO LIVER TRANSPLANT RECIPIENTS

EXPRESSIVE DYSPHASIA POSSIBLY RELATED TO FK506 IN TWO LIVER TRANSPLANT RECIPIENTS

Phenylketonuria: MR imaging of the brain with clinical correlation.

Fifteen patients with biochemically documented phenylketonuria (PKU) were studied with use of magnetic resonance (MR) imaging with spin-echo T2-weighted pulse sequences. The resulting images demonstrated varying degrees of symmetric high signal intensity of the white matter within the posterior cerebral hemispheres. Involvement of the anterior hemispheres was seen only in cases with severe signal intensity changes. There was no involvement of the cerebral cortex, brain stem, or cerebellum. Moreover, no anatomic structural abnormalities were observed. Mild cortical atrophy was observed in eight of the 15 patients. There was no significant correlation between the patients' IQ scores and the level of MR signal intensity changes. Although MR imaging routinely shows relatively distinct abnormalities in patients with PKU, the clinical severity of the disease does not parallel its imaging severity.

Neuropathology of Rett syndrome.

Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: (1) diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; (2) mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; (4) immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; (5) ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; (6) preliminary biochemical studies revealed increased beta-endorphines in thalamus and cerebellum; (7) peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance.

On the white matter lesions of the Creutzfeldt-Jakob disease: Can a new subentity be recognized in man?

One case of CJD with severe involvement of the white matter is discussed. The patient was admitted after a 3-month clinical course with rapidly increasing mental deterioration, coma vigil-like state, myoclonic twitching of the limbs and of the facial muscles. The EEG showed the typical features of CJD. The first CT scan, performed 3 months after onset, revealed only a mild cortical and subcortical atrophy of the brain. The second CT scan, 12 months later, showed a considerable cortical and subcortical atrophy of the brain. The patient died 18 months after onset. Neuropathological examination showed a severe degeneration in the gray matter, with spongiosis, loss of neurones and hypertrophic glial reaction. The white matter was also involved with severe spongiosis, demyelination and hypertrophic glial proliferation. The case is discussed in relation to the data in the literature. It is argued that cases of CJD with severe involvement of the white matter should be classified as a new neuropathological subentity of CJD.