Folia Psychiatrica et Neurologica Japonica, Vol. 26, No. 1, 1972
A Sporadic Case of Cerebral Lipidosis in an Adult (Kufs) -Pathological and Histochemical Findings-
Hiroshi ISHINO, M.D. Department of Neuropsychiatry, Okayama University Medical School, Okayama
Hiroshi ISHIZU, M.D. and Keisuke SARAI, M.D. Department of Neuropsychiatry, Hiroshima University School of Medicine, Hiroshima
After considering several diagnoses, it was decided that a 42 year-old female, whose illness had lasted at least 15 years, was suffered from amaurotic idiocy.
The present report is concerned with the clinical and anatomical features of a spo- radic case of adult type (Kufs) of this dis- ease. The clinical course was characterized by dementia, myoclonia, cerebellar signs and muscular rigidity. The major histologic features were enlargement of neurons by lipid deposits. The histochemical investiga- tions were also carried out and the results will be presented.
CASE REPORT K.S., a married female aged 42 year-old
at the time of death. No history of family disease of the nervous system. Previous personal history not significant. After good performance in a primary school and a girls high school, the patient became a school- teacher. She had married at the age of 27. She was a person of few words, gentle and diligent.
The present illness began in 1955, when she was 27 years. Soon after the marriage, husband and family noticed a change in her behaviour-she became apathetic, disinter-
Received for publication March 8. 1972.
ested in her surroundings, did not prepare the meal and clear the table. When her house was on fire, she lay indifferently in bed. When the husband asked her to help to put out a fire, she replied calmly that it was not she who had set fire to the house, and refused to help.
Since 1957 she has been forced to change school in secluded place every one year, be- cause she became inadequate to the post of teacher.
From April 1961, she began to stumble on several occasions, and consulted a doc- tor. In June of the same year she retired from school. Afterwards speech difficulties slowly developed.
The first investigation (Neuropsychiatric Clinic, Hiroshima University), in August 1963, revealed tremor of the hands. Whilst speaking, her voice stopped suddenly sev- eral times. Epilepsy was suspected,
Subsequently tic-like cramp of the lower jaw appeared, and speech difficulty progres- sively worsened. Reinvestigation, in Janu- ary 1965, showed the following findings: fasciculation of the tongue, marked finger tremor, muscular rigidity and exaggeration of the deep reflexes. Parkinsons disease was then suspected, and anticholinergic drugs were administered. In the evening of the same day, a generalized convulsion was
56 H. Ishino, H. Ishizu and K. Sarai
noted. In April of the same year, an EEG showed a very irregular basic activity with high voltage slow wave bursts accompanied with paroxysmal spikes. With a provisional diagnosis of epilepsy, anticonvulsants were added to anticholinergic drugs without ef- fect. In July of the same year, muscle cramp of the lower limbs as well as pulsion phenomenon was noted. In October she was observed to be having small absence which lasted several seconds. In Novem- ber tic-like movements aggravated and her walking became more unsteady. Intention tremor also appeared. She was admitted, in December 1965, on suspicion of brain organic lesion. Two days after admission, opisthotonus accompanied with loss of con- sciousness was noted. Afterwards she be- came bedridden but was discharged from the Clinic without amelioration in her con- dition.
She was re-admitted in April 1966. Ex- amination on admission revealed clonic twitchings of the facial muscles including the upper eyelids and coarse fibrillation of the tongue. Her muscles of four limbs were found hypotonic and there were sudden rhythmic contractions of all four limbs re- sembling myoclonias, which were dominant in the distal portions of both upper and lower extremities. Outstretching forwards of both upper limbs was impossible for her, because of jerky lowering of the upper limbs. Deep reflexes were hyperactive on both sides, but neither clonus nor abnormal re- flexes were noted. Co-ordinate movements were impaired and Holmes-Stewart rebound phenomenon was positive. Sensation ap- peared normal. General examination re- vealed no physical abnormality.
Psychiatric examination revealed the fol- lowing findings: The patient was apathetic, facial expression was mask-like. She re-
mained euphoric, and showed no interest in her surroundings. Comprehension was markedly impaired, and she replied to all questions Yes. Disorientation, amnesia, memory disturbance and confabulation were noted. She was childlike, laughed without reason and sometimes displayed frenzy. From time to time she was incontinent.
The puls, blood pressure, and tempera- ture were normal. The blood picture, blood chemistry and liver function tests were all normal. Wassermann reaction of both blood and CSF was negative. EEG records made on April 25, 1966 were poor in a- waves and showed marked dysrhythmia. Ocular fundi and X-ray of the skull were normal. The air-encephalogram showed a slight enlargement of the third ventricle and a moderate enlargement of the lateral ven- tricles.
In July 1966 she was transfered to an- other hospital. Afterwards she continued to deteriorate. In February she died of pneu- monia at the age of 42 years. The illness lasted about 15 years.
Autopsy findings of the brain. Macroscopic findings : The brain weighed
900 g. Meninges were normal and on coronal sections there was nothing relevant aside from a moderate enlargement of the lateral ventricles.
Microscopic findings: The cerebral cortex in Nissl preparations was normal in cyto- architecture and there was only some loss of the nerve cells. The prominent feature was the swelling of the nerve cells extend- ing over the more or less entire nervous system (Fig. 1 ) . Their nuclei were clear and well preserved, but displaced to the base of apical dendrite by the storage sub- stance. Nissl substance was dissolved and the cytoplasm was homogeneously blue, i.e. they showed the change of Schaffer-Spiel-
A Sporadic Case of Cerebral Lipidosis in an Adult (Kufs) 57
Table 1 . Histochemical characteristics of storage substance in the nerve cells of the frontal cortex
Lipid Sudan 111 orange Oil red reddish-brown Sudan black B yellowish-black Nile blue bluish-black
Okamotos sulphuric-acetic acid
Okamotos mercuric nitrate
Okamotos separation test
(for cholesterin) (-1
(for glycolipids) (-)
(for phospholipids and cerebroside) ( + I
(for sphingomyelin) ( + I
Bial (for neuraminic acid) (-1
meyer (Fig. 2). This was marked in the third, fifth and sixth layer of the cerebral cortex. In PAS preparations, cytoplasm of the neurons was filled with brightly red small granules. Around the nuclei of the small nerve cells of the second and fourth layer there were densely PAS-positive gran- ules. These granules were also found around the nuclei of the astrocytes. In Bodian preparations, the neurofibrillae were opressed to the periphery of the cell body and the cytoplasm was filled with granular materal (Fig. 3). This storage material was unstained by the Sugamo-Heidenhain method for myelin, and stained a orange with Sudan 111. Holzer stain did not show fibrous gliosis in the cerebral cortex and white mat- ter. In the occipital cortex, only the scat- tered larger neurons of the fifth layer were distended.
In the basal ganglia, the nerve cells of the lateral nuclei of the thalamus showed a moderate swelling. In the striatum, some loss of the large neurons was noted, the re- maining nerve cells were irregular in shape
and showed hyperchromatosis. In the pal- lidum, only a slight degree of swelling of the nerve cells was noted. Holzer stain showed a slight fibrous gliosis in the an- terior nuclei of the thalamus and in the pallidum.
In the mid brain, the neurons of the sub- stantia nigra and oculomotor nuclei showed a similar change and were filled with PAS- positive substance. Particularly in the sub- stantia nigra, Nissl stain revealed loss of melanin pigments and the cytoplasm of the nerve cells was covered by the relatively large granules stained blue.
In the pons, the change was marked and the neurons of the pontine nuclei were balooned by the lipid material, which was yellow with H-E. stain. The eccentric nuclei showed pycnosis (Fig. 4). In addition Holzer stain showed a moderate fibrous gliosis.
In the medulla oblongata, these changes were also noted. The nuclei of the nerve cells showed pycnosis and Nissl stain re- vealed a diffuse homogeneous blue. There
58 H. Ishino, H. Ishizu and K. Sarai
was fibrous gliosis (Fig. 5) . The nerve cells of the hypoglossal nuclei and the reticular formation were slightly balooned and showed chromatolysis.
In the cerebellum, the base of the den- drite of Purkinje cell was distended and filled with yellow granular material in H-E. preparations (Fig. 6 ) . In Bodian prepara- tions, the basket fibers were well preserved. The granular layer was almost normal. The nerve cells of the dentate nuclei showed marked swelling, and in Holzer preparations a slight gliosis in the arca surrounded by the dentate nuclei was observed.
In the spinal cord, there was some loss of the anterior horn cells and the remaining neurons showed a moderate enlargement.
Histochemical investigations of the stor- age substance in the nerve cells of the fron- tal cort