Huntington ' s disease . Abnormal MRI signal in the rigid form of

888 Journal of Neurology, Neurosurgery, and Psychiatry 1991;54:888-891 M Savoiardo, L Strada, D Oliva, F Girotti, L D'Incerti Abstract Eighteen patients with Huntington's disease (HD) were examined with MRI. Eleven had the common hyperkinetic form, seven had the rigid variant. All seven patients with rigid HD had increased signal intensity in the neostriatum in intermediate and T2-weighted images. Only one hyperkinetic HD had similar findings. In all the other cases, signal abnormalities were questionable or absent. Histological differences that account for differences in signal intensity may therefore lie in the caudate nucleus and putamen. Age of onset may be important, since the rigid patients were younger. Follow up studies may help in understanding these signal differences. Departments of Neuroradiology and Neurology,* Istituto Nazionale Neurologico "C Besta", Milan, Italy M Savoiardo L Strada D Oliva* F Girotti* L D'Incerti Correspondence to: Dr Mario Savoiardo, Department of Neuroradiology, Istituto Nazionale Neurologico "C Besta", Via Celoria 11, 20133 Milan, Italy Received 16 July 1990 and in final revised form 20 December 1990. Accepted 9 January 1991 the neostriatum in T2-weighted images at 1-5 T was described by Rutledge et al in four cases, consistent with increased iron content.4 We have recently observed high signal intensity in T2-weighted images in cases with the rigid variant of HD. We report a series of patients with HD, in which we compare the signal abnormalities of the cases with the rigid variant versus the cases with the classic hyperkinetic form. Methods We reviewed a series of 18 patients with HD. Eleven patients had the typical hyperkinetic form and seven had the rigid variant. All the patients had a family history of HD, as proved by examination of other affected members of the family and a review of medical records. Diagnosis of rigid HD was made according to Bruyn and Went's criteria, when a definite Huntington's disease (HD) is a disabling rigidity was observed. To our knowledge, no degenerative disease with autosomal dominant necropsy had been performed on other meminheritance, clinically characterised by bers of the affected families. Of the 11 hyperkinetic HD patients, seven involuntary hyperkinesia, affective-emotional disturbances and intellectual deterioration, were males, and four females. Age ranged usually beginning between 35 and 45 years of from 17 to 63 years (mean 45-2 years); disease duration ranged from one to 14 years (mean age. HD clinical features may be variable and an atypical form mainly characterised by plas5 1 years). tic rigidity and a Parkinsonian-like posture Of the seven rigid HD patients, three were has been described.' This "rigid" variant of males, four females. Age ranged from 14 to 47 HD is more common in young patients, but years (mean 28-8 years). Disease duration similar cases have also been observed in ranged from three to nine years (mean 5 7 adults. The classic hyperkinetic HD may years). These patients presented rigidity and often evolve toward an akinetic state.' bradykinesia. In three subjects, postural Gross pathological changes include diffuse tremor was observed; in four cases, mild cerebral atrophy and, more characteristically, hyperkinesia involved face and distal segatrophy of the striatum. The head of the ments of the limbs. caudate nucleus shrinks considerably and the Physical disability was estimated by the profile of the frontal horn of the lateral ven- Shoulson and Fahn rating scale.5 Mean (SD) tricle therefore becomes flattened. The disability rating was 6-42 (3 55) for the rigid putamen is also reduced in size, and, less form, and 7 09 (3 20) for the hyperkinetic commonly and to a lesser degree, the pallidum form. may be affected.2 All patients were studied with MRI 05 T. Atrophy of the head of the caudate nucleus One patient with the rigid form was also with enlargement of the frontal horn, the most examined with a 1-5 T unit. All the examinacharacteristic aspect of HD, was demonstrated tions included sagittal Ti-weighted images in vivo even by pneumoencephalography. It is and transverse SE intermediate and T2demonstrated by CT and MRI. Density chan- weighted images. Occasionally Tl-weighted ges have not been reported on CT, nor has images in coronal or transverse planes were abnormal increased signal intensity been available. reported on MRI studies.34 MRI is better for demonstrating, in transverse and in coronal sections, the atrophy of the head of the Results caudate nucleus. No signal abnormalities are All patients presented with atrophy, both difmentioned in a series of 12 patients with HD fuse and focal, particularly involving the head by Kido et al;3 decreased signal intensity in of the caudate nucleus (fig 1). No differences J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.10.888 on 1 October 1991. Downloaded from http://jnnp.bmj.com/ on December 11, 2021 by guest. Protected by copyright. Abnormal MRI signal in the rigid form of Huntington's disease 889 Abnormal MRI signal in the rigid form of Huntington's disease Figure 2 (A) Hyperkinetic HD in a 43 year old female. No abnormal signal intensity in T2-weighted image (SE 1933/100). (B) Rigid HD in a 23 year oldfemale. Slightly increased signal intensity in T2-weighted image (SE 2100/100), (arrows). (C) and (D) Intermediate and T2weighted images (SE 2100/50, 100) in a 28 year old male with rigid HD; increased signal intensity in the neostriatum (arrows) is more evident. i J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.10.888 on 1 October 1991. Downloaded from http://jnnp.bmj.com/ on December 11, 2021 by guest. Protected by copyright. Figure I HD, hyperkineticform. (A) Severe atrophy of the head of the caudate nucleus (arrowheads) in coronal section in a 42 year old male. (B) Atrophy of the putamen (arrowheads) in transverse section in a 57 year oldfemale. No signal abnormalities in both cases (SE 2100/ 50); compare the signal intensity of the neostriatum with that of the insular cortex. Savoiardo, Strada, Oliva, Girotti, D'Incerti 890 Discussion There are various observations about the histological differences between rigid and hyperkinetic HD. Dom et alP reported an almost complete loss of the smaller small cell population and an outfall of large neurons of the striatum in the rigid form. Conversely, Bugiani et al,7 emphasised the survival of large striatal neurons in the rigid variant; this form could be the expression of the inhibition of the substantia nigra resulting from an unbalanced striatal output. The importance of pallidal lesions have also been advocated to explain rigidity in HD.89 It is generally accepted, however, that the neuronal loss is more marked in the putamen in the patients with the rigid form, in whom a global putaminal volume loss is more evident.2810 The presence of more extensive damage in rigid HD Figure 3 Coronal sections in a 43 year old female with hyperkinetic HD (A), and in a 24 year old male with rigid HD (B), (SE 100). Signal hyperintensity is present in the putamen (arrows) and caudate nucleus (arrowheads) only in the rigid patient. 19337 has been recently confirmed by immunohistochemical studies; these studies demonstrated that, in the rigid variant, striatal neurons projecting both to the lateral and medial segments of the pallidum are lost, while in the hyperkinetic form the projections to the medial globus pallidus are preserved.'0 In our series of patients, MRI constantly demonstrated increased signal intensity in intermediate and T2-weighted images in the caudate nucleus and in the putamen in the patients affected by the rigid form of HD. With one exception, this signal abnormality was not seen or was very mild or questionable in the hyperkinetic HD patients. Signal hyperintensity in intermediate and T2-weighted images is consistent with increased amounts of water, therefore compatible with cell loss or gliosis. In the only rigid case studied with 1-5 T magnet, hyperintensity was seen, just as in the 05 T study. No hypointensity in T2-weighted images consistent with increased iron content was demonstrated in this patient, as reported by Rutledge et al in four cases.4 According to our data, it seems that the histological differences between rigid and hyperkinetic HD lie in the neostriatum and that the importance of changes in the pallidum or other locations should probably be excluded. There are no differences in disease duration and disability scale between the two different forms that account for the signal abnormalities. It will be extremely interesting to observe follow up MRI studies for the possible development of signal abnormalities in the hyperkinetic patients, if some of them become akinetic. The younger age of the patients with the rigid variant might also have some importance in determining the high signal intensity, since the only patient with equal hyperintensity in the hyperkinetic group was the youngest subject of this latter group. In fact, it has been J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.10.888 on 1 October 1991. Downloaded from http://jnnp.bmj.com/ on December 11, 2021 by guest. Protected by copyright. in severity of atrophy were found between the two groups of hyperkinetic versus rigid HD patients. All patients with the rigid form of HD presented signal abnormalities consisting of mild to moderate hyperintensity in the caudate nucleus and putamen in intermediate weighted images and, all but one, also in T2-weighted images. The single study performed at 1-5 T showed signal hyperintensity in the neostriatum, more marked in the putamen, as the 0-5 T examination had demonstrated. In the group of typical hyperkinetic HD, only one patient, a 17 year old man with a two year history of the disease, presented signal hyperintensity in the neostriatum similar to that demonstrated in the patients with the rigid variant. Two other patients presented a milder hyperintensity in the neostriatum. The other eight patients had normal signal intensity except for occasional, questionable hyperintensity in the neostriatum only in intermediate weighted images but normal signal intensity in T2-weighted images (figs 2 and 3). Abnormal MRI signal in the rigidform of Huntington's disease We thank Dr F Tagliavini, neuropathologist, for his helpful comments. This study was partly supported by a grant of the Associazione Italiana Corea di Huntington. Presented in part at the 42nd annual meeting of the American Academy of Neurology, Miami Beach, Florida USA, May 1990. 1 Bruyn GW, Went LN. Huntington's chorea. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of clinical neurology, Vol 5 (49): Extrapyramidal disorders. Amsterdam: Elsevier, 1986:267-314. 2 Roos RAC. Neuropathology of Huntington's chorea. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of clinical neurology, Vol 5 (49): Extrapyramidal disorders. Amsterdam: Elsevier, 1986:315-26. 3 Kido DK, Shoulson I, Manzione JV Jr, Harnish P. High field strength MRI scans in patients with Huntington's disease. AJNR 1987;8:934. 4 Rutledge JN, Hilal SK, Silver AJ, Defendini R, Fahn S. Study of movement disorders and brain iron by MR. AJNR 1987;8:397-411. 5 Shoulson I, Fahn S. Huntington's disease: clinical care and evaluation. Neurology 1979;29:1-3. 6 Dom R, Baro F, Brucher JM. A cytometric study of the putamen in different types of Huntington's chorea. In: Barbeau A, Chase TN, Paulson GW, eds. Huntington's chorea 1872-1972. Advances in neurology, Vol 1. New York, Raven Press, 1973;369-85. 7 Bugiani 0, Tabaton M, Cammarata S. Huntington's disease: survival of large striatal neurons in the rigid variant. Ann Neurol 1984;15: 154-6. 8 Campbell AMG, Corner B, Norman RM, Urich H. The rigid form of Huntington's disease. J Neurol Neurosurg Psychiatry 1961;24:71-7. 9 Jellinger K. Degenerations and exogenous lesions of the pallidum and striatum. In: Vinken PJ, Bruyn GW, eds. Diseases of the basal ganglia. Amsterdam, North-Holland, 1968;6:632-93. 10 Albin RL, Reiner A, Anderson KD, Penney JB, Young AB. Striatal and nigral neuron subpopulations in rigid Huntington's disease: implications for the functional anatomy of chorea and rigidity-akinesia. Ann Neurol 1990;27:357-65. 11 Myers H, Vonsattel JP, Stevens TJ, et al. Clinical and neuropathologic assessment of severity in Huntington's disease. Neurology 1988;38:341-7. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.54.10.888 on 1 October 1991. Downloaded from http://jnnp.bmj.com/ on December 11, 2021 by guest. Protected by copyright. reported that the forms of HD with juvenile onset are associated with a more marked cell loss and atrophy of the neostriatum." In conclusion, the signal hyperintensity in the neostriatum described here is not exclusively observed in the rigid form of HD, but seems to be a characteristic of this variant; it is very rare in the classic hyperkinetic form. 891