morning glory sign: a particular mr finding in progressive

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*Corresponding author, Phone:＋81-23-641-6419, Fax: ＋81-23-641-5203, E-mail: miadchi＠beach.ocn.ne.jp

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Magnetic Resonance in Medical Sciences, Vol. 3, No. 3, p. 125–132, 2004

MAJOR PAPER

Morning Glory Sign: A Particular MR Finding inProgressive Supranuclear Palsy

Michito ADACHI1*, Toru KAWANAMI2, Humi OHSHIMA3, Yukio SUGAI4,and Takaaki HOSOYA4

1Department of Radiology, 3Department of Neurology, Ohshima Clinic4-1-14, Sakurada Nishi, Yamagata 990-2321, Japan

2Third Department of Internal Medicine, 4Department of Radiology,Yamagata University School of Medicine

2-2-2 Iidanishi, Yamagata 990-9585, Japan(Received September 21, 2004; Accepted December 15, 2004)

Background and Purpose: We have encountered a peculiar atrophic change in themidbrain in some patients with parkinsonian syndromes. We discovered these patients hadvertical supranuclear gaze-palsy, an eye movement disorder. The purpose of this study wasto elucidate whether this atrophic pattern of the midbrain (which we have termed morningglory sign) is related to the vertical eye movement disorder, in particular to progressivesupranuclear palsy (PSP).

Methods: We reviewed T2-weighted axial images obtained from 42 patients withparkinsonian syndromes, including ˆve patients with PSP, 23 patients with Parkinson'sdisease, and 14 patients with multiple system atrophy (MSA). We focused on a speciˆcatrophy of the midbrain, the morning glory sign, which is a concavity of the lateral marginof the tegmentum of the midbrain.

Results: The morning glory sign was detected in four of the ˆve patients with PSP and inone (striatonigral degeneration; SND) of the14 patients with MSA. All morning glory signpatients had vertical supranuclear gaze-palsy, as did the one PSP patient without themorning glory sign. Vertical supranuclear gaze-palsy was seen in no other patients(23 patients with Parkinson's disease and 13 patients with MSA) who lacked the morningglory sign.

Conclusions: Morphologically, the morning glory sign is believed to be related to verticalsupranuclear gaze-palsy. This sign should be considered a useful clue when diagnosingPSP.

Keywords: magnetic resonance imaging, brain, parkinsonian syndrome, progressivesupranuclear palsy

Introduction

Progressive supranuclear palsy (PSP, or Steele-Richardson-Olszewski syndrome), an adult-onsetneurodegenerative disorder, is characterized byearly postural instability and vertical supranucleargaze-palsy. Clinically, it is important to diŠerenti-ate PSP from other patients with parkinsoniansyndromes (Parkinson's disease and multiplesystem atrophy)1–4, because the e‹cacy of drugssuch as levodopa against PSP is diŠerent (poor or

absent response) from that against Parkinson'sdisease. Furthermore, with disease progression,dementia as well as parkinsonism should eventuallyoccur in PSP. Recently, a measurement of themidbrain was reported to be a clue for discriminat-ing PSP patients from Parkinson's disease andmultiple system atrophy (MSA).5–7

On the other hand, in our experience, we found apeculiar atrophy of the midbrain in some patientswith parkinsonian syndromes, and those patientshad vertical supranuclear gaze-palsy. This atrophy,characterized by a concavity of the lateral marginof the tegmentum of the midbrain, we have termedthe morning glory sign, because the shape of the

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Table 1. Progressive supranuclear palsy

No. Age(years) Gender Duration of illness

(years) Clinical ˆndings

1 59 male 2 Rigidity, dyskinesia, vertical supranuclear palsy2 65 male 1 Rigidity, dyskinesia, gait disturbance, cerebellar ataxia,

vertical supranuclear palsy3 75 male 6 Rigidity, dyskinesia, dysphagia, dementia,

vertical supranuclear palsy4 78 female 3 Rigidity, postural instability, gait disturbance,

vertical supranuclear palsy5 81 male 3 Tremor, gait disturbance, incontinence,

vertical supranuclear palsyMean 71.6±9.3 3±1.9

126 M. Adachi et al.

Magnetic Resonance in Medical Sciences

midbrain resembles a lateral view of the morningglory ‰ower.

We retrospectively assessed the relationshipbetween the morning glory sign and verticalsupranuclear gaze-palsy in patients with parkinso-nian syndromes in order to elucidate whether it is areliable MRI (magnetic resonance imaging) ˆndingon which to base a diagnosis of PSP. At the sametime, we evaluated abnormal signals of the mid-brain in T2-weighted images.

Subjects and Methods

SubjectsWe examined 12 normal volunteers (four men

and eight women aged 53 to 79 years; meanstandard deviation, 67.9±7.1 years) withoutneurological deˆcit, ˆve PSP patients (four menand one woman, aged 59 to 81 years; meanstandard deviation, 71.6±9.3 years), 23 patientswith Parkinson's disease (11 men and 12 womenaged 46 to 78 years; mean standard deviation,63.7±9.4 years) and 14 patents with MSA (six menand eight women aged 53 to 75 years; meanstandard deviation, 64.6±7.2 years). The MSAgroup comprised eight patients with olivopon-tocerebellar atrophy (OPCA) and six patients withstriatonigral degeneration (SND).

All the controls were apprised of the purpose ofthe MR examination and all provided informedconsent. The patients were diagnosed by neu-rologists between 1996 and 2003. Those withPSP were diagnosed according to criteria of theNational Institute of Neurological Disorders andStroke and the Society for Progressive Supra-nuclear Palsy (NINDS-SPSP).8 The diagnosis ofParkinson's disease was based on clinical criteria,including the following neurological signs: restingtremor, rigidity, bradykinesia, disorder of pos-tural re‰ex, and good response to levodopa or

anticholinergic therapy. The diagnosis of MSA wasbased on clinical signs: autonomic disorders,cerebellar ataxia, parkinsonism, and MR ˆndings(atrophy of the cerebellum, pons, middle cerebellarpeduncle and putamen, and an abnormally highintensity of the pons, middle cerebellar peduncleand putamen in T2-weighted images). Patients withhereditary spinocerebellar degeneration diagnosedthrough genetic analysis were excluded. The clinicalinformation on the patients is summarized inTables 1–4.MR imaging

All controls and patients underwent the MRstudy with a 1.5T superconducting system (Signa;General Electric, Milwaukee, WI, U.S.A.). Inorder to evaluate the morphological change in themidbrain and signal changes such as abnormal highintensity around the aqua duct, we obtainedT2-weighted axial images that were parallel to theplane and which included the ponto-medullaryjunction and the nasion. This imaging method is aroutine imaging technique and was not speciallydesigned for this study.

T2-weighted imaging was performed with fastspin-echo imaging under the following parameters:relaxation time, 3,540 ms; echo time, 105 ms; FOV,28×28 cm; slice thickness, 6 mm; slice gap, 1.5mm, 512×256 matrix; 2 NEX, 2 min 8 s forT2-weighted images; echo train length for T2-weighted fast spin echo images, 12.Assessment of the lateral margin of the tegmentumof the midbrain

We focused on T2-weighted axial images of themidbrain, including the mammillary body.

When assessing the lateral margin of the tegmen-tum of the midbrain, we drew a transverse linerunning through the posterior edge of the aquaduct, and set point A where the transverse linecrossed the lateral margin of the midbrain. Point Bwas set at the pit between the tegmentum and the

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Table 2. Parkinson's disease


(years)Hoehn-Yahrclassiˆcation

1 46 male 10 22 49 male 7 33 53 male 1 24 53 female 3 25 55 female 2 26 56 male 8 27 57 male 6 48 59 female 4 39 59 female 7 1

10 59 male 5 411 60 male 23 412 66 female 12 413 66 female 5 314 67 female 16 415 70 female 7 416 71 male 2 217 71 male 18 418 73 female 10 319 73 male 10 120 74 female 15 421 74 female 1 222 77 male 2 223 78 female 9 4

mean 63.7±9.4 8.0±5.8 G1, 2; G2, 8; G3, 4; G4, 9*

*Grade of Hoehn-Yahr classiˆcation

Table 3. Multiple system atrophy (olivopontocerebellar atrophy, OPCA)



1 53 female 1 Cerebellar ataxia, gait disturbance2 54 male 1 Gait disturbance3 62 female 1 Gait disturbance, dysphonia4 64 female 1 Cerebellar ataxia5 67 male 6 Hypotension, incontinence, gait disturbance, dementia6 67 female 1 Vertigo, gait disturbance, dysphonia7 72 male 2 Gait disturbance8 75 female 1 Cerebellar ataxia

Mean 64.3±7.8 1.8±1.8

127A Particular MR Finding in PSP

Vol. 3 No. 3, 2004

cerebral peduncle.We then judged the lateral margin of the tegmen-

tum of the midbrain to be convex when the lateralmargin ran on or outside the straight line betweenpoints A and B (Fig. 1a). When the lateral marginof the midbrain ran inside the line between pointsA and B, we judged the margin to be concave(Fig. 1b).

The concave appearance of the lateral margin ofthe tegmentum of the midbrain was called the

morning glory sign. Two observers (M. A., Y. S.)with no prior knowledge of the patients' status(patient or control subject) independently assessedthe lateral margin of the midbrain with a personalcomputer.

Results

The morning glory sign was observed in four ofthe ˆve patients with PSP (Fig. 2) and in one of the

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Table 4. Multiple system atrophy (striatonigral degeneration, SND)



1 53 male 2 Vertigo, cerebellar ataxia, decline of perspiration2 61 male 1 Vertigo, rigidity, incontinence, vertical supranuclear palsy3 68 female 1 Gait disturbance, rigidity4 68 female 4 Dyskinesia, gait disturbance, incontinence5 69 female 7 Tremor of upper limbs, gait disturbance6 72 male 13 Rigidity, dyskinesia

Mean 65.2±7.0 4.7±4.7

Fig. 1.a: A schema of an axial section of the normal midbrain at the mammillary body level. Point A is thepoint at which the transverse line running through the edge of the aqua duct crosses the lateral mar-gin of the midbrain. Point B is the pit between the tegmentum and the cerebral peduncle. The lateralmargin of the normal tegmentum runs on or outside the straight line between points A and B.b: A schema of the morning glory sign (the concave appearance of the lateral margin of thetegmentum of the midbrain). The lateral margin of the tegmentum runs inside the straight linebetween points A and B. This morphological change in the midbrain resembles a lateral view of themorning glory ‰ower.



14 patients with MSA (SND). The MSA patient andall PSP patients with the morning glory sign hadvertical supranuclear gaze-palsy. However, the onePSP patient without the morning glory sign (caseNo. 2, a 65-year-old male patient) also presentedwith vertical supranuclear gaze-palsy.

However, the morning glory sign was seen inneither the controls nor in other patients [23patients with Parkinson's disease (Fig. 3) and 13patients with MSA (Figs. 4, 5)]. Moreover, thesepatients did not have vertical supranuclear gaze-palsy. No discrepancies arose between the twoobservers in estimating the morphological changesof the midbrain.

The abnormal high intensity around the aquaduct in T2-weighted images was not seen in anycontrol subject or patient with Parkinson's disease,OPCA or SND. This area of abnormal highintensity was seen in only one of the ˆve patients

with PSP (case No. 5, an 81-year-old male patient,Fig. 6).

Discussion

The NINDS-SPS (National Institute of Neuro-logical Disorders and Stroke and the Society forProgressive Supranuclear Palsy) diagnostic criteriafor possible PSP indicate a gradually progressivedisorder with an onset at age 40 or later, eithervertical supranuclear palsy or both a slowing ofvertical saccades and postural instability with fallswithin a year of onset.8 Although the criteriaoutline the physical characteristics of PSP well, asmentioned in previous studies there have beenmany di‹culties in discriminating PSP from otherparkinsonian syndromes (Parkinson's disease andMSA).1–4 In particular, the presence of verticalsupranuclear gaze-palsy is signiˆcantly helpful in

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Fig. 3.a: A 59-year-old male with Parkinson's disease (Hoehn-Yahr classiˆcation: 4). The lateral marginof the posterior tegmentum of the midbrain is convex (arrows).b: The lateral margin of the tegmentum of the midbrain runs outside the line between points Aand B.

Fig. 2.a: A 75-year-old male with PSP. A T2-weighted axial image of the midbrain shows the concaveshape of the lateral margin of the posterior tegmentum (morning glory sign, arrows).b: The lateral margin of the tegmentum of the midbrain runs inside the line between points A and B.


Vol. 3 No. 3, 2004

diagnosis, but physicians must bear in mind thatthis physical sign can take several years to developin some patients.

Many of the MRI ˆndings documented forparkinsonian syndromes have shown in Parkin-son's disease a reduction in the width of thehyperintense band (the pars compacta of the sub-

stantia nigra)9–13 and low-signal intensity of theputamen, globus pallidus, and substantia nigra inT2-weighted images.14–16 However, many otherreports contradict these ˆndings.11–13,16–18 Thus,there seems to be a lack of reliable MRI ˆndingswith which to diagnose this neurological disorder.

The signs of PSP on MRI are the following:

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Fig. 5.a: A 68-year-old female with SND. In a T2-weighted image, mild atrophy of the entire midbrain is evident;however, the lateral margin of the posterior tegmentum of the midbrain is convex (arrows).b: The lateral margin of the tegmentum of the midbrain runs outside the straight line between points Aand B.c: A T2-weighted image shows atrophy and abnormal high intensity of the bilateral putamen (whitearrow).

Fig. 4.a: A 62-year-old female with MSA (OPCA). A T2-weighted image shows neither atrophy of the midbrainnor abnormal high intensity. The lateral margin of the posterior tegmentum is convex (arrows).b: The lateral margin of the tegmentum of the midbrain runs outside the line between points A and B.c: A T2-weighted image shows mild atrophy of the pons, middle cerebellar peduncle, and cerebellum.Cruciform high intensity of the pontine base (white arrow) and abnormal high intensity of the middlecerebellar peduncle (black arrow) are also evident.



atrophy of the tegmentum of the midbrain andsuperior colliculus, narrowing of the pars compactaof the substantia nigra, abnormal high intensity ofthe gray matter around the aqua duct, and mildcerebral atrophy.5,17,19,20 The high-intensity of thegray matter around the aqua duct, one of thecharacteristics of PSP, does not always appear.This ˆnding was seen in only one of our ˆve casesof PSP. Therefore, the high intensity of the graymatter around the aqua duct is a speciˆc but notsensitive marker for PSP diagnosis.

The MRI ˆndings for OPCA, which is varianceof MSA, are atrophy of the pontine base andcerebellar hemisphere, and the cruciform high-intensity in the pontine base and abnormal high-intensity in the middle cerebellar peduncle onT2-weighted images.19–22 Then, those for SND areatrophy and variable abnormal signal intensity inthe putamen.21,22 In some patients with SND, whichis also variance of MSA, atrophy of the pons andcerebellum, and the cruciform high-intensity of thepontine base on T2-weighted images are seen.22

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Fig. 6. An 81-year-old male with PSP. A T2-weighted image shows the morning glory sign of themidbrain (black arrows). This T2-weighted imagealso visualizes abnormal high intensity around theaqua duct (white arrow).


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As stated above, many MRI ˆndings regardingparkinsonian syndromes have been described;however, these ˆndings do not occur consistently inevery patient. Consequently, it is di‹cult todiscriminate PSP from Parkinson's disease andMSA, especially in the early stages. Recent MRIˆndings of parkinsonian syndromes have indicatedthat a low midbrain diameter may be valuable indiscriminating PSP from Parkinson's disease andMSA.6,7 However, the values overlap with those ofthe latter disorders.6,7

We retrospectively reviewed MRI ˆndingsobtained from patients with Parkinson's disease,PSP, and MSA in order to investigate themorphological characteristics of the midbrain inparkinsonian syndromes. A peculiar atrophy of themidbrain has been seen in patients with PSP andMSA who had progressive supranuclear gaze-palsy.This atrophic change, a concavity of the lateralmargin of the midbrain, we named the morningglory sign because the shape of the midbrainresembled a lateral view of the morning glory‰ower.

Pathologically, PSP is characterized by thedestruction of subcortical structures including theglobus pallidus, subthalamic nucleus, substantianigra, gray matter around the aqua duct, superiorcolliculus, Edinger-Westphal nucleus, nucleus inter-stitial Cajal, pretectal area, cuneiform nucleus,and rostral interstitial nucleus of the medial

fasciculus.23–25 These structures are mainly locatedin the cranial and dorsal part of the midbrain.Large numbers of neuroˆbrillary tangles, neuropilthreads, and tufted astrocytes are also found withinthese brain regions.23 These inclusions comprise in-soluble aggregates of tau phosphoprotein.23 On theother hand, in MSA degeneration of the olivopon-tocerebellum (the transverse pontine ˆbers andpontine neurons), striatonigral and autonomic sys-tems are seen; however, degeneration of the graymatter around the aqua duct and superior collicu-lus does not occur.26,27 The midbrain usuallyshrinks not only in PSP, but also in MSA.However, in the present study, the lateral margin ofthe midbrain in four of the ˆve PSP patients wasconcave (the morning glory sign) and that of almostall patients with MSA remained convex. Only oneof the 14 patients with MSA, who had rigidity,incontinence, vertigo, and vertical supranuclearpalsy, showed the morning glory sign. The morningglory sign may re‰ect degeneration of the cranialand dorsal part of the midbrain, which is one of theimportant pathological characters of PSP. In nopatient with Parkinson's disease did we see atrophyof the midbrain. Although this study included onlyˆve patients with PSP, from these results we believethat a strong relationship exists between the con-cave appearance of the tegmentum of the midbrain(the morning glory sign) and vertical supranucleargaze-palsy.

Most recently, A. Righini et al. published aninteresting report regarding morphological changesin the midbrain of patients with PSP.28 Theydemonstrated that a ‰at or concave superior proˆleof the midbrain in midsagittal T1-weighted imagesmight be useful in the diagnosis of PSP. We alsobelieve that this MRI ˆnding may be useful in theclinical diagnosis of parkinsonism; however, thepathological changes mentioned above betterexplain the morning glory sign than the concavesuperior proˆle of the midbrain.

Conclusion

The morning glory sign, a peculiar MRI ˆndingof midbrain atrophy, seems to appear in PSP andSND patients with vertical supranuclear gaze-palsy.This sign may be useful in the diagnosis of PSP.

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