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Panencephalopathic Type of Creutzfeldt-Jakob Disease: Primary Involvement of the Cerebral White Matter

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Panencephalopathic Type of Creutzfeldt-Jakob Disease: Primary Involvement of the Cerebral White Matter J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.44.2.103 on 1 February 1981. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry, 1981, 44, 103-115 Panencephalopathic type of Creutzfeldt-Jakob disease: primary involvement of the cerebral white matter TOSHIO MIZUTANI,* ATSUSHI OKUMURA,t MASAYA ODA,j AND HIROTSUGU SHIRAKI§ From the Clinical Neuropathology, Tokyo Metropolitan Institute for Neurosciences, Fuchu,* the Department of Psychiatry, School of Medicine, Osaka City University,t the Department of Neuropathology, Institute of Brain Research, School of Medicine, University of Tokyo,: and the Shir-aki Institute of Neuropathology, Tokyo, Japan§ S U M M A R Y Eight necropsy cases of a "panencephalopathic" type of Creutzfeldt-Jakob disease (CJD) in the Japanese are reported. The reasons why this type should be discussed separately from other types of CJD are that there is primary involvement of the cerebral white matter as guest. Protected by copyright. well as the cerebral cortex, and that the white matter lesion of one Japanese human brain with CJD similar to the present group has been successfully transmitted to experimental animals. Creutzfeldt-Jakob disease (CJD) is a diffuse de- 1000 g, irrespective of the duration of the clinical generation of the central nervous system usually course (5 to 30 months). This finding differs from occurring in middle age and fatal within two previous reports that the brain atrophy in CJD is years. Clinical variations are numerous, but the only mild to moderate in degree and increases with most common picture includes severe mental de- the duration of illness.5 terioration, rigidity of muscles and myoclonic jerks. Neuropathological alterations, are wide- Clinical findings spread and variable, but are confined to the The patients were six males and two females. The age cortical and subcortical grey matter. The white at death was from 47 to 73 years, (average of 58), and matter is considered never to be a main site of the disease occurred particularly in the 5th and 6th pathology, although demyelination or myelin pallor decades. The total duration of illness was approxi- mately 5, 7, 75, 8-5, 9 and 11 months, and 2 years of the white matter has been described infre- and 2-5 years. Most ran a subacute clinical course quently in some reported cases1 2; such involve- within one year, except cases 7 and 8 which continued ment has been interpreted as secondary to neuronal for 2 years and 2-5 years, respectively. All cases http://jnnp.bmj.com/ disintegration.3 were sporadic, without significant hereditary factors, The eight necropsy cases of CJD described here and no precipitating cause was evident. There were showed severe and extensive degeneration of the three stages in the clinical course: the initial or pro- cerebral white matter which could not be explained dromal stage, the intermediate stage of rapid neuro- simply as secondary to cortical deterioration.4 logical and mental deterioration, and the terminal Such cases with prominent lesions of white matter vegetative state (fig 1). have not so far been described from western The initial stage was characterised by insidious onset of various physical and psychotic complaints, such as countries. This severe involvement of the white headache, fatigability, loss of appetite, restlessness on September 26, 2021 by as well as the grey matter explains the marked and mental slowness in most cases, but in cases 2 and decrease in brain weight, which was usually below 6 the initial disturbance was a sudden onset of diplopia. In case 8, gradually increasing tremor of the hands Address for reprint requests: Dr Mizutani, Department of Clinical was the first complaint. During this stage, numbness Neuropathology, Tokyo Metropolitan Institute for Neurosciences, ascending from the legs to the arms occurred in case 1 2-6 Musashidai, Fuchu-City 183, Japan. and hand tremor in case 4. This stage lasted for two Accepted 30 August 1980 weeks or less. 103 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.44.2.103 on 1 February 1981. Downloaded from 104 Toshio Mizutani, Atsushi Okumura, Masaya Oda, and Hirotsugu Shiraki Table Clinical picture of the present group of CJD Case I Case 2 Case 3 Case 4 Case S Case 6 Case 7 Case 8 Age (yr) 47 55 63 73 62 56 56 49 Sex F M F M M M M M Duration (M) 5 7 7.5 85 9 11 24 30 Dementia + + + + + + + Focal signs + + + + Perservation + + + Hallucinations + + + or delusions + + Psychomotor excitement + + Akinetic mutism + + + + + + + Pyramidal signs amyotrophy + + + + + Rigidity + + ~+ + Myoclonic jerks + + + + + + + Tremor + Choreo-athetoid + + Gait disturbance/ataxia + + + ~~~+ + + + Romberg's sign + + + + + + Dysarthria + Convulsions + + ~~~~+ + + Sensory disturbance + + Visual disturbance + Para-, tetraplegia in flexion/ + + + + + + + extension PSD + + + + + + + + Brain weight (Grams) 1200 980 990 1100 1100 930 1200 760 (+) =Present. PSD=Periodic synchronous discharge. guest. Protected by copyright. ~,,Ri4 Jt The intermediate stage was of rapid deterioration with neurological and mental disturbances developing one after another and the patients eventually becoming a.dS e : .., .......... hypokinetic and mute. Although the onset of this stage 47 F ME Akirwe MiU11... was not always obvious, rapid development of gait disturbance predominated in cases 1, 2, 5 and 6, while m dementia preceded the manifestation of gait disturb- Case 2 s - Muscuidit 55M s ance in case 7. Gait disturbance developed sooner or PIara TetraO5e,i later in all cases, but it was difficult to decide whether FaIeXK)nxtensin it was of pyramidal, extrapyramidal or cerebellar MAf::o!-k^>cieriC . origin... Ataxic gait was observed in cases 1, 2, 4, 5 and Case 3 :_ 0. 63 F 6 and Romberg's sign was evident in cases 1 and 6. *-A Subsequent rapidly progressive development of mus- cular rigidity of all extremities soon rendered the lase 4 patients bedridden. Myoclonic jerks and muscular 73M rigidity developed in all cases; convulsive seizures of grand mal type subsequently occurred in cases 6 and 7. In case 3, on the other hand, myoclonus was only CaJse5 observed in the terminal stage, while convulsions oc- ----, .---- curred in the intermediate stage. Periodic synchronous http://jnnp.bmj.com/ discharges on EEG were recorded before or after the manifestation of myoclonus in all cases. ---------------------- -------- CJase 6 i :: Tremulous movements of hands were observed in 5i M 1 manifested in five cases I ".. cases and 4. Dysarthria .. IA"-:-.. (cases 1, 2, 4, 5 and 6), but there still remained the question whether this was related to brainstem or C-56,e ... ....... ... ... ................. cerebellar involvement. Generally speaking, typical 56 M symptoms and signs of cerebellar involvement never comprised a main feature in any of the patients, even on September 26, 2021 by when severe cerebellar involvement was found post- ........ ..4... ........... ............. ...... -. mortem. Pyramidal signs and symptoms, such as hyper- 49 M. active deep tendon reflexes and pathological reflexes, fi2M were observed in cases 1, 4 and 5, while neurogenic muscular atrophy was never encountered. Choreo- Fig 1 Clinical course of the pres;ent group of CJD. athetoid movements were found in cases 1, 5 and 6. Arrow indicates the onset of the odisease. The main psychic disturbance was progressive de- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.44.2.103 on 1 February 1981. Downloaded from Panencephalopathic type of Creutzfeldt-Jakob disease 105 mentia. Various cerebral focal signs, such as aphasia, progression of global dementia. In addition, psycho- apraxia and agnosia, also were observed, although motor excitement, delusion and visual hallucination they were sooner or later superseded by steady rapid occurred transiently during the course of illness. -.._ .-, X',O~~~AWA ,~, - , * l'- C Wty *,~~~~~~~ guest. Protected by copyright. '4k~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~4 !~~~ ~ ~~~ 4* i@~t%~ < . ~~~ . ; ,> 8 ., ''.^x...... iW etq,h; <e x*f l ty -S - Mr~~~~~ e,,, ;\ N '.n X i,4n. 4 4.*~\5*a 5.i0 A a'.-XX't~~~~~~~~~~~~~~~~5f..'. *~~~~~~~~~~~~~~~~4e~'*14. ~~~~~~~7~~ ~ ~ ~ ' $z71 .*+*~~~~~~4,,7. '~ ~ ~~~~. http://jnnp.bmj.com/ d ,~~~~~~~~~ tV1A.~~~~~~~~~~'-a Fig 2 a: Cerebral cortex of the frontal pole. Severe cortical atrophy, particularly in the depths and walls of the conspicuously dilated sulci (case 6). b: Frontal cortex in the wall of the sulcus. Severe neuronal loss, conspicuous proliferation of astrocytes and sieve-like tissue loosening in almost all layers, except the molecular layer. 1: The molecular layer; 2: The second layer; 3: The third layer; Sc: Subcortical white matter on September 26, 2021 by (case 6). c: Frontal cortex in the depth of the sulcus. Pronounced tissue destruction of laminar distribution in almost all layers, except the molecular layer (case 8). d: Temporal cortex. Microcystic coalescent cavitations in almost all layers, except for the molecular layer, continuously involving the subcortical white matter (case 8). e: Frontal cortex at the crown of the gyrus. Comparatively well preserved neurons in contrast to proliferated astrocytes. Inflated neurons in the deeper layers (arrows) (case 6). f: Deeper layer of insular cortex. Marked inflated neuron with an eosinophilic intracytoplasmic inclusion (case 3). [a, b, c, d, e and f: H & E; a: X4-8; b: X64; c: X64; d: X32; e: X64; f: X640]. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.44.2.103 on 1 February 1981. Downloaded from 106 Toshio
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