Diffuse Lewy Body Disease Presenting with a Supranuclear Gaze Palsy

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Joutrnial of Neurology, Neurosurgery, and Psychiatry 1991;54:159-161 159 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.2.159 on 1 February 1991. Downloaded from SHORT REPORT

Diffuse Lewy body disease presenting with a supranuclear gaze palsy

J M Fearnley, T Revesz, D J Brooks, R S J Frackowiak, A J Lees

Abstract rigidity, hypomimia and in the limbs he had A patient with diffuse Lewy body disease cogwheel rigidity, bradykinesia and an presented with supranuclear vertical occasional rest tremor with a left sided and horizontal ophthalmoplegia, demen- preponderance. The tendon reflexes were tia, axial rigidity and falls, bradykinesia brisk in the legs with bilateral Babinski signs. and pyramidal signs. This broadens the There was a disturbance of recent memory clinical presentation of this pathological and features suggesting a temporoparietal diagnosis and re-emphasises the hetero- defect: nominal dysphasia, dyscalculia, geneity of patients diagnosed clinically as occasional right-left disorientation and mild progressive supranuclear palsy (Steele- constructional dyspraxia. Richardson-Olszewski syndrome). On formal psychometry, however, there was cognitive deterioration affecting a wide range of skills including tests sensitive to Diffuse Lewy body disease (DLBD)' is clin- frontal lobe dysfunction. His verbal IQ was 99 ically characterised by the combination of (WAIS) compared with a premorbid IQ of Parkinsonism, dementia and psychiatric sym- 115 (National Adult Reading Test). CT scan- ptoms.2 At presentation, however, the patient ning revealed generalised cortical atrophy. usually has only one of these symptoms mak- There was no response to a trial of levodopa. ing a definite clinical diagnosis impossible. During the following two years and six mon- Even at necropsy, the diagnosis is often ths, he developed a tendency to lean back- overlooked, because of the difficulty in visual- wards with frequent falling and his mobility ising cortical Lewy bodies on routine stains gradually worsened to a point where he could and the presence of Alzheimer changes, only walk with the assistance of two people. especially neuritic plaques, sometimes con- There was further cognitive deterioration sidered to be secondary to DLBD.' The com- with episodic confusion and hallucinations. bination of Parkinsonism and dementia is not He developed a dressing apraxia, visuospatial exclusive to DLBD and may occur in the defect, Broca's type dysphasia and severe Steele-Richardson-Olszewski syndrome dysarthria. He died of bronchopneumonia (SRO), which is characterised by supra- three years after the onset of his illness. http://jnnp.bmj.com/ nuclear ophthalmoplegia, pseudobulbar palsy, axial dystonia in extension, dementia and bradykinesia.45 Early in the disease only one Pathological examination component may be prominent, but most At necropsy he was found to have bilateral would agree that for a diagnosis to be at all lower lobe bronchopneumonia and a right certain a supranuclear downgaze palsy is pulmonary artery embolus. The fixed brain

essential. We describe a case of DLBD, which weighed 1300g and there was generalised on September 27, 2021 by guest. Protected copyright. presented like SRO with Parkinsonism, gyral atrophy and bilateral pallor of the sub- dementia, ophthalmoplegia, dysarthria, axial stantia nigra and the locus coeruleus. Blocks rigidity, pyramidal signs and failure to res- were taken from representative cerebral, pond to levodopa. brainstem and cerebellar areas. The sections were stained with haematoxylin and eosin, luxol fast blue/cresyl violet,. Bielschowsky National Hospital for Case History silver impregnation and anti-ubiquitin Nervous Diseases, Queen Square, This 71 year old man was initially admitted immunostain. Neurofibrillary tangles and London with urinary frequency for two years and neuritic plaques (demonstrated by Bielschow- J M Fearnley recently associated with incontinence; a cysto- sky silver method) and Lewy bodies (anti- T Revesz D J Brooks metrogram was compatible with an unstable ubiquitin immuno-stain) were counted in RSJ Frackowiak bladder. In addition, he gave a six month seven micron sections of the hippocampus, A J Lees history of generalised slowing of movement, frontal and temporal cortex. In each cortical a area of Correspondence to: falls, failing memory, a soft voice and dif- region rectangular Dr Lees, National Hospital ficulty in swallowing. He was seen by two of 7-12 mm2 was outlined and counted using an for Nervous Diseases, the Queen Square, London the authors (DJB and RSJF) who found a eyepiece graticule with parallel sweeps of WC1N 3BG, UK supranuclear ophthalmoplegia with poor microscope stage. There were flame shaped Received 12 February 1990 voluntary and pursuit movements in both ver- tangles, mature neuritic plaques and Lewy and in final revised form 18 June 1990. tical and horizontal directions and intact doll's bodies in the cerebral cortex (fig la and table). Accepted 6 July 1990 eye movements. He also had severe axial Tangles were confined to the allocortex and 160 Fearnley, Revesz, Brooks, Frackowiak, Lees J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.2.159 on 1 February 1991. Downloaded from Figure la Cortical Lewy bodies in two neurons of layer V of the temporal cortex, Ubiquitin x 150. lb Brainstem Lewy bodies in the paramedian pontine reticular formation, haematoxylin and eosin, x 700.

Figure 2 Co-existent Lewy bodies and neurofibrillary tangle neuron of the dorsal-vagal motor nucleus, Bielschowsky, x 1000.

medial longitudinal fasiculus and the nucleus

,,~~*Wfi:.~~~ .f:: of Darkschewitsch appeared normal with no intraneuronal inclusions. Other areas typically involved in SRO were normal.

Discussion The presence of a supranuclear gaze palsy, axial rigidity, early dementia and failure to respond to levodopa led to the diagnosis of SRO in this patient. Clinically, there was a .q~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~suggestion that the dementia was predomin- Table Neurofibrillary tangle, Lewy body and neuritic plaque counts (number per mm2) antly of a temporoparietal type, which would not be in keeping with this diagnosis.8 Region Tangle Lewy body Plaque However, neuropsychological testing revealed global cognitive dysfunction with marked Frontal 0 3 3 8-5 0 2 0 14-9 impairment of tests sensitive to frontal lobe Temporal Ti 0 3 9 31 1 dysfunction. Testing, as with SRO, was hin- T2 0 1 1 4-8 T3 0 2-8 5 7 dered by the ophthalmoplegia. As the disease Hippocampus 7 3 2 1 14 8 progressed the dementia became more severe Subiculum 5 0 1 4 9-2 Entorhinal 91 2-8 131 than that usually seen in SRO. The cornerstone in the diagnosis of SRO is the presence of a supranuclear gaze palsy, but Lewy bodies were more widely distributed this has also been described in a number of neocortex a other multisystem degenerations including including the with predilection for http://jnnp.bmj.com/ the temporal gyri and the deeper cortical one case of DLBD.89 Furthermore, a transient layers. Neuritic plaque counts fulfilled Kha- supranuclear palsy associated with infection chaturian's diagnostic criteria for Alzheimer's has been described in two cases of Parkinsons's disease.6 There was a correlation between the disease'0 and pathological changes have been numbers of neuritic plaques and Lewy bodies found in nuclei involved in the control of eye (r = 0-85, p < 0-01), but not between movements: nucleus of Darkschewitsch, ros- neuritic plaques and tangles. The nucleus tral interstitial nucleus of the medial long- basalis of Meynert was considerably atrophic itudinal fasciculus, interstitial nucleus of Cajal on September 27, 2021 by guest. Protected copyright. with severe neuronal loss and there was also and periaqueductal grey matter." nerve cell loss, free pigment and gliosis in the In our case the prominent findings were substantia nigra, locus coeruleus and dorsal neuritic plaques and NFTs in the vagal motor nucleus. The distribution of cell periaqueductal grey matter and Lewy bodies loss in the substantia nigra was typical of in the pontine paramedian reticular formation. Parkinson's disease being greatest in the In this limited study we were unable to come caudal ventrolateral cell groups.7 Tangles to a conclusion as to the pathological basis of were absent in the nucleus basalis of Meynert, the ophthalmoplegia. Possible responsible but were present in the brainstem nuclei sites could be the frontal eye fields, although less frequently than Lewy bodies, periaqueductal grey matter (vertical gaze) and 20 times less in the substantia nigra and four pontine paramedian reticular formation times less in the locus coeruleus. In the dorsal (horizontal gaze). It has been suggested that vagal motor nucleus, one neuron was found lesions of the rostral interstitial nucleus of the which contained both inclusions, (fig 2). Lewy medial longitudinal fasiculus cause a vertical bodies were found in the pontine paramedian gaze palsy and whether it is up or down is reticular formation, (fig lb), and tangles and determined by the medio-lateral extent of the neuritic plaques were found in the lesion. 12 periaqueductal grey matter. The IIIrd, IVth It has also been shown that a lesion of the and VIth nerve nuclei, the interstitial nucleus interstitial nucleus of Cajal may cause a ver- of Cajal, the rostral interstitial nucleus of the tical gaze palsy and nuchal dystonia in exten- Diffitse Lewy body disease presenting with a supranuclear gaze palsy 161 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.2.159 on 1 February 1991. Downloaded from sion in cats.' The gaze palsy, however, may nuclear palsy. Arch Neurol 1964;10:333-59. 5 Kristensen MO. Progressive supranuclear palsy-20 years be secondary to destroying fibres from the later. Acta Neurol Scand 1985;71:177-89. rostral interstitial nucleus of medial 6 Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch the lon- Neurol 1985;42:1097-105. gitudinal fasciculus passing through the inter- 7 Hassler R. Zur Pathologie der Paralysis Agitans und des stitial nucleus of Cajal. Postenzephalitischen Parkinsonismus. 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Annals Neurol 1985;18: 136-7. features of diffuse cortical Lewy body disease (Lewy body 12 Buttner-Ennever JA, Buttner U, Cohen B, Baugartner G. dementia). Brain 1987;110:1 131-54. Vertical gaze paralysis and the rostral interstitial nucleus 3 Lennox G, Lowe J, Landon M, Byrne EJ, Mayer RJ, of the medial longitudinal fasiculus. Brain 1982;105: Godwin-Austin RB. Diffuse Lewy body disease: cor- 125-49. relative neuropathology using anti-ubiquitin immuno- 13 Fukushima-Kudo J, Fukushima K, Tashiro K. Rigidity and cytochemistry. J Neurol Neurosurg Psychiatry 1989; dorsiflexion of the neck in progressive supranuclear palsy 52:1236-47. and the interstitial nucleus of Cajal. J Neurol Neurosurg 4 Steele JC, Richardson JC, Olszewski J. Progressive supra- Psychiatry 1987;50:1 197-203. http://jnnp.bmj.com/ on September 27, 2021 by guest. Protected copyright.