Radiological quiz
Dec 21st, 2009 by Administrator

The author: Professor Yasser Metwally


December 21, 2009 — Radiological quiz

Slide show 1. Radiological quiz…What is your diagnosis

Click here to download the answer in PDF format

Click here to view cases with similar diagnosis

Click here to view the MRI version of the case


  1. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 11.1a January 2010 [Click to have a look at the home page]
Spinal-Dural Arteriovenous Fistulas: A treatable cause of myelopathy frequently overlooked
Dec 14th, 2009 by Administrator

The author: Professor Yasser Metwally


December 14, 2009 — Spinal-dural arteriovenous fistulas are the most common variety of spinal cord AVM.[1] Spinal-dural arteriovenous fistulas are thought to be acquired lesions,[1] occur mainly in older adults (mean age of 51 years), and are found more often in men than women. Patients present with slowly progressive myelopathy and radiculopathy,[2,3] which, if left untreated, can progress to paraparesis or quadriparesis. (Click to download a case record in PDF format)  (Click to view all case records under the title “arteriovenous fistula” in

The arteriovenous fistula is located in the dura itself. The feeding vessels are nonradicular branches of the spinal arteries, small, tortuous arterioles that originate from the dura. The feeding arteries are generally normal in caliber and flow through these lesions is exceptionally slow. A single draining radicular vein is often at the level of the spinal root foramina. The vein is dilated many times the size of the artery and flows retrograde into the anterior and posterior medullary veins and coronal venous plexus surrounding the spinal cord. Chronic venous hypertension and stagnation result in chronic medullary ischemia.[4]

Although phase contrast MR I [5] or dynamic gadolinium-enhanced MR I [6] may increase detection, in our experience these small connections can be easily missed even on excellent quality MRI images. Serpiginous flow voids around the cord may represent flow in dilated medullary veins. The spinal cord may also be enlarged, and intramedullary increased signal on T2-weighted images may represent edema or ischemia secondary to venous hypertension.

Slide show 1. MRI showing  dilated perimedullary veins (due to dural spinal arteriovenous fistula) and congestive myelopathy demonstrated as central cord edema (Central cord T2 hyperintensity) and spinal cord enlargement. The central cord hyperintensity is taking the shape of the central grey matter

Contrast myelography in both the supine position, which can best demonstrate the retromedullary veins, and the prone position reveals dilated and tortuous veins over the dorsum of the cord. If dilated veins are observed, complete spinal angiography is indicated. Image quality must be the best possible to delineate the origin of the shunt. Filming should continue into the late venous phase up to several seconds after the injection.

The majority of patients with the fistula in the thoracic and lumbar region have arterial supply independent of the supply to the spinal cord. Internal iliac artery supply was observed in 12.5% of cases.[7] Endovascular embolization with liquid adhesive can frequently cure these lesions. Initial apparently successful embolization was achieved in 90% of 20 patients in one study; the fistula recurrence rate (failure to occlude the draining vein) for N-butyl cyanoacrylate (NBCA) was 15% (3 patients). All patients who underwent embolization had either improved (55%) or unchanged (45%) gait disability at last follow-up.[8] Not infrequently, complete clinical cure can be achieved in cases presenting with a nonfixed, moderate, neurologic deficit. Recanalization has occurred in cases in which PVA was used as the primary therapy.[9] Open surgery is recommended if embolization fails to occlude the dural arteriovenous fistula.

Slide show 2. Spinal angiography (same patient as in slide show 1) Showing the spinal dural arteriovenous fistula before and after embolization


  1. Rosenblum B, Oldfield EH, Doppman JL, Di Chiro G. Spinal arteriovenous malformations: a comparison of dural arteriovenous fistulas and intradural AVM’s in 81 patients. J Neurosurg 1987;67:795-802
  2. Merland JJ, Riche MC, Chiras J. Intraspinal extramedullary arterio-venous fistulae draining into the medullar veins. J Neuroradiol 1980;7:271-320
  3. Koenig E, Thron A, Schrader V, Dichgans J. Spinal arteriovenous malformations and fistulae: clinical, neuroradiological and neurophysiological findings. J Neurol 1989;236:260-266
  4. Kataoka H, Miyamoto S, Nagata I, Ueba T, Hashimoto N. Venous congestion is a major cause of neurological deterioration in spinal arteriovenous malformations. Neurosurgery 2001;48:1224-1229; discussion 1229-1230
  5. Mourier KL, Gelbert F, Reizine D, et al. Phase contrast magnetic resonance of the spinal cord preliminary results in spinal cord arterio-venous malformations. Acta Neurochir (Wien) 1993;123:57-63
  6. Thorpe JW, Kendall BE, MacManus DG, McDonald WI, Miller DH. Dynamic gadolinium-enhanced MRI in the detection of spinal arteriovenous malformations. Neuroradiology 1994;36:522-529
  7. Larsen DW, Halbach VV, Teitelbaum GP, et al. Spinal dural arteriovenous fistulas supplied by branches of the internal iliac arteries. Surg Neurol 1995;43:35-40; discussion 40-41
  8. Song JK, Gobin YP, Duckwiler GR, et al. N-Butyl 2-cyanoacrylate embolization of spinal dural arteriovenous fistulae. AJNR Am J Neuroradiol 2001;22:40-47
  9. Nichols DA, Rufenacht DA, Jack CR Jr, Forbes GS. Embolization of spinal dural arteriovenous fistula with polyvinyl alcohol particles: experience in 14 patients. AJNR Am J Neuroradiol 1992;13:933-940
  10. Spinal dural arteriovenous fistula [Full text]
  11. Arteriovenous Malformations/Fistulas of the Cervical Spinal Cord [full text]
Radiological quiz
Dec 13th, 2009 by Administrator

The author: Professor Yasser Metwally


December 13, 2009 — Radiological quiz

  Slide show 1. Radiological quiz…What is your diagnosis

Click here to download the answer in PDF format


  • Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 11.1a January 2010 [Click to have a look at the home page]
Case record: progressive supranuclear palsy (PSP)
Dec 8th, 2009 by Administrator

The author: Professor Yasser Metwally


December 8, 2009 — A 61-year-old man with gait difficulty, frequent falls, akinetic rigidity, and hypophonic speech.

A 61-year-old retired painter presented with 2-year history of increasing difficulty with initiation of gait. He had frequent falls with a tendency to topple backward. He developed a soft growling speech, apraxia of eyelid opening, and symmetric bradykinesia. He sometimes cried inappropriately but his cognitive function was otherwise thought to be normal. He had no family history of neurologic disorder.

Examination revealed positive applause sign, utilization behavior, and a positive bilateral grasp and palmomental reflex, a staring appearance with reduced blinking, apraxia of eyelid opening, hypophonic dysarthria, supranuclear up and down gaze palsy, and axial rigidity. He walked with a broad-based shuffling gait and the pull test was positive. His symptoms did not improve with L-dopa treatment.

  • Neuroimaging

This elderly man had an atypical parkinsonian syndrome characterized by early postural instability and falls backward, a vertical supranuclear gaze palsy, axial rigidity, pseudobulbar palsy, frontal lobe signs, and a poor response to L-dopa. These are characteristic features of progressive supranuclear palsy (PSP), also known as Richardson disease. It has a prevalence of 5 per 100,000, but is commonly underdiagnosed. The clinical features are quite different from PD or other atypical parkinsonian syndromes such as MSA. However, there is a subgroup of progressive supranuclear palsy (PSP), patients, known as PSP-Parkinsonism (PSP-P), which presents with asymmetrical bradykinesia, jerky tremor, and an initial L-dopa response without vertical gaze palsy. Other unusual presenting features of progressive supranuclear palsy (PSP), include primary gait freezing, early frontotemporal dementia, and corticobasal syndrome.

MR imaging of the brain can be normal in the early stages of disease. Nevertheless, certain MR imaging features can greatly assist in making the diagnosis especially in patients with PSP-P or an atypical presentation (Fig. 1). The first radiological clue for progressive supranuclear palsy (PSP), would be the presence of striking hyperextension of the neck on sagittal MR imaging. The characteristic MR imaging feature is selective atrophy of the midbrain in association with preservation of the pons. The resulting atrophy of the midbrain tegmentum gives a distinctive concavity with the appearance of the beak of a hummingbird or king penguin, and is termed the “hummingbird” [48] or “penguin” sign (see Fig. 1A). [49] Quantitative measurements of midbrain atrophy have been shown to improve diagnostic accuracy of PSP. Midbrain diameter in PSP (13.4 mm) was shown to be significantly lower than that of PD (18.5 mm). [48] Recent study indicated that the surface area of midbrain of progressive supranuclear palsy (PSP), (56 mm2) was significantly smaller than that of Parkinsonian subtype of MSA (MSA-P) (97.2 mm2), PD (103 mm2), and healthy controls (117 mm2). Some overlaps of the area measurements were observed in PSP and Parkinsonian subtype of MSA (MSA-P), but the ratio of the area of the midbrain to pons was significantly smaller in PSP when compared with Parkinsonian subtype of MSA (MSA-P). [49]

Click to enlarge figure

Figure 1. (A) Sagittal T1-MR imaging demonstrates volume loss in the midbrain with relative preservation of the pons. The midbrain tegmentum has lost its normal convexity giving it the appearance of a hummingbird (or penguin), also known as the “hummingbird sign.” (B) T2-weighted axial MR imaging demonstrates “Mickey mouse” or “morning glory” sign with concavity of the lateral margin of midbrain tegmentum. (Click to enlarge figure)

On axial views, the selective atrophy of the midbrain tegmentum with relative preservation of the tectum and cerebral peduncles produces the “Mickey mouse” sign (see Fig. 1B). Sometimes, the concavity of the lateral margin of the midbrain tegmentum is referred to as the “morning glory” sign and has high specificity but rather low sensitivity for PSP.

Other radiological findings of PSP include dilatation of the third ventricle, particularly the posterior portion, signal change in the periaqueductal gray matter indicative of gliosis, and atrophy of the superior cerebellar peduncle, which has a specificity of 94% and sensitivity of 74% and can aid the differentiation of PSP from MSA-P and PD. [51] “Eye of the tiger” sign with hypointensity signal change in T2, a common finding in pantothenate kinase-associated neurodegeneration (PKAN), can occasionally be observed in PSP, indicating the presence of iron deposition in the putamen.[52]

  • Discussion

Progressive supranuclear palsy (PSP), also known as Steele-Richardson-Olszewski syndrome, is a neurodegenerative disease that affects cognition, eye movements, and posture. PSP was first described as a clinicopathologic entity in 1964. Characteristics include supranuclear, primarily vertical, gaze dysfunction accompanied by extrapyramidal symptoms and cognitive dysfunction. The disease usually develops after the sixth decade of life, and the diagnosis is purely clinical. Currently, no proven effective therapy exists. The cause of PSP remains unknown. Most cases appear to be sporadic. Both environmental and genetic influences have been postulated. (Click for more details) (Click for more details)

PSP is usually fatal within approximately 6 years of onset, with a range of 2-17 years, based on cohort patients dying under surveillance; life table analysis among Golbe’s entire cohort [13,14,15,16] revealed a median disease duration of 9.7 years. Conflicting reports exist regarding the influence of age at diagnosis on survival; Younger patients usaully survive longer, although this is not a uniform finding among other studies [13,36]

The primary causes of death in patients with PSP are infections and pulmonary complications (eg, pneumonia) that are frequently related to immobility. Often, the primary morbidity relates to imbalance leading to immobility, although dementia, visual symptoms, and dysphagia are major concerns. Approximately 50% of patients with PSP require some aid to walk within 3 years of the initial symptoms. The interval from initial symptom occurrence to the need for a cane or a walker is 3.1 years, and the interval to confinement to a chair or bed is 8.2 years.



The first clinicopathologic descriptions of PSP were published in 1963 and 1964 and proved to be remarkably accurate. Only in the past 15 years have neurologists and basic scientists again focused on this disorder.

The onset of PSP is insidious, and usually a prolonged phase of vague fatigue, headaches, arthralgias, dizziness, and depression occurs. Patients also develop subtle personality changes, memory problems, and pseudobulbar symptoms, and family members are often a more accurate source of such information than the patient. The initial symptoms can often involve unexplained imbalance or falls. Over time, dysarthria, dysphagia, and visual symptoms ensue.

In a neuropathologic study, the most common symptoms at disease onset were postural instability and falls (63%); dysarthria (35%); bradykinesia (13%); and visual disturbances such as diplopia, blurred vision, burning eyes, and light sensitivity (13%).

The cardinal manifestations of PSP are supranuclear ophthalmoplegia; pseudobulbar palsy; prominent neck dystonia; parkinsonism; behavioral, cognitive, and gait disturbances that cause imbalance; and frequent falls.

Although presentations vary and early predominance of a particular symptom is not unusual, a greater spectrum of symptoms inevitably ensues over time. Several other features have been reported, including sleep disturbance with insomnia, clumsiness, impaired handwriting, and oscillopsia. Although the full constellation of symptoms occurring in a progressive fashion over time is characteristic, the vertical gaze palsy is the most distinctive single clinical feature.

Other features that can be prominent include focal or segmental dystonia in the form of limb dystonia or blepharospasm.

Patients can also have asymmetric apraxia resembling corticobasal degeneration.

Micturition disturbances, including urinary incontinence, are common in the later stages.


The physical examination emphasizes the clinical features previously outlined. PSP is characterized primarily by motor, cognitive, and visual symptoms. Documentation of cognitive function with attention to executive function is important.

The cranial nerve examination should include detailed analysis of ocular motility.

Slow vertical saccades and square wave jerks are early signs in most patients. The classic gaze palsy in PSP is supranuclear ophthalmoplegia. Supranuclear in this context refers to a lesion above the ocular motor nuclei, thus sparing the ocular motor nuclei, nerve fascicles, and neuromuscular junctional and extraocular muscles. Examination features serve to establish that the infranuclear structures are intact and that the lesion lies within the supranuclear domain. A supranuclear vertical gaze limitation is improved following extravolitional pathway activation, such as the vestibular ocular reflex (VOR) or the Bell phenomenon.

The Bell phenomenon consists of upward eye deviation behind closed lids. This can be assessed clinically by partially holding the eyelid open and instructing the patient to try forcefully closing the eye. The vertical VOR can be activated by manually flexing and extending the neck while the patient views a distant target. If the extent of the vertical eye movement limitation is improved with either of these maneuvers, then the lesion is supranuclear in origin.

Measurement of ocular alignment in the cardinal positions of gaze at near and distance viewing often discloses the source of any diplopic symptoms.

Examination of the eyelid position and movements may yield critical information.

The characteristic facies, especially when associated with dysarthria, may provide a nearly pathognomonic clinical picture.

Examination of pursuit movements and the extent of ocular rotations are important.

Often, the earliest symptoms relate to imbalance and dysarthria. The imbalance is part of an extrapyramidal syndrome that is inclusive of poor postural reflexes, axial greater than appendicular rigidity, and dysarthria (monotone with slight hypophonic quality). Resting tremor is unusual.

The early appearance of gait and balance dysfunction is in contrast to the course of idiopathic Parkinson disease, in which imbalance tends to occur late in the disease. The gait in individuals with PSP tends to be wider based and unstable; these individuals have a tendency to fall in any direction because of impaired postural reflexes.

Bradykinesia with masked facies and a startled expression are frequent findings. Retrocollis may be present; with lid retraction, it enhances the astonished, worried appearance. Increased rigidity without cogwheeling or tremor completes the motor picture.

Visual symptoms tend to be a relatively early finding, but they may not be present at onset; rarely, they are absent entirely. The earliest eye sign often is slowing of vertical saccades and fast phases. Later, the classic vertical supranuclear ophthalmoparesis occurs; this typically involves downgaze before upgaze. As a supranuclear process, vertical eye movements can still be generated by the VOR until late in the course of the disease, although the Bell phenomenon is usually absent (supraduction with eye closure). Later in the disease course, this ophthalmoparesis affects horizontal, in addition to vertical, eye movements. Complete ophthalmoparesis may ensue late in the course.

Additionally, nearly continuous square wave jerks are commonly observed with fixation. Square wave jerks consist of small (<5°) horizontal movements that take the eyes conjugately off target and then return the eye to the target after a brief 180- to 200-millisecond latency. Although occasional square wave jerks are a common finding in elderly individuals and may be normal if unaccompanied by other symptoms, more continuous square wave jerks are often associated with an underlying CNS disease.

Convergence eye movements are often impaired, and convergence insufficiency may produce episodic diplopia at near distances. Impaired binocular fusional capacity may produce diplopia related to decompensated phorias. Impaired VOR suppression has also been noted.

Several eyelid signs frequently occur in individuals with PSP, including lid retraction, eyelid opening or closing apraxia, blepharospasm, or lid lag.

Loss of the fast component of the optokinetic nystagmus can precede gaze palsy.

Cognitive dysfunction and personality change are common, but they are generally milder in degree compared to primary dementing illnesses such as Alzheimer disease. Slowed cognitive processing, sequencing and planning difficulties, mild memory difficulty, and apathy are typical. These are generally more prominent later in the disease course.

Litvan and Mega et al [27] discussed the neuropsychiatric aspects of PSP in greater detail. The investigators administered the Neuropsychiatric Inventory (NPI) to 22 patients with PSP, 50 patients with Alzheimer disease, and 40 controls.

The NPI focuses on the presence of delusions, hallucinations, agitation, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, and abnormal motor behavior.

The presence of high apathy scores coupled with low agitation and anxiety scale scores was used to correctly identify patients with PSP 85% of the time.

Litvan and Agid et al [25] tested the accuracy of 4 proposed clinical diagnostic criteria for PSP. These authors applied the proposed diagnostic criteria to autopsy-proven cases, including 24 cases of PSP, 29 cases of Lewy body disease, 10 cases of cortical-basal ganglionic degeneration, 7 cases of postencephalitic parkinsonism, 16 cases of multiple system atrophy, 7 cases of Pick disease, and 12 cases of other parkinsonian or dementing illnesses.

None of the criteria demonstrated both high sensitivity and high predictive value. A regression analysis approach revealed that vertical supranuclear palsy with downgaze abnormalities and postural instability with unexplained falls were the most useful diagnostic features.

A progressive disease course including these features constituted the mandatory inclusion criteria. Mandatory exclusion criteria included a history of encephalitis, hallucinations, cerebellar signs, noniatrogenic dysautonomia, unilateral dystonia, alien hand syndrome, early cortical dementia, or focal lesions on examination or imaging. These criteria performed better than previously published guidelines, with a mean sensitivity of 57% and positive predictive value of 85%. When applied to data from the patient’s last visit to clinic, the criteria revealed a sensitivity of 66% and positive predictive value of 76%.

The participants in a National Institute of Neurological Disorders and Stroke (NINDS)/Society for PSP conference formulated clinical research criteria for the diagnosis of PSP. They based these new criteria on literature review and then validated them using a clinical data set from autopsy-confirmed cases of PSP.

Criteria for possible PSP are as follows:

  • Gradually progressive disorder with onset when the individual is aged 40 years or older
  • Either vertical supranuclear palsy or both slowing of vertical saccades and prominent postural instability with falls in the first year of onset
  • No evidence of other diseases that can explain the clinical features

Criteria for probable PSP are vertical supranuclear palsy with prominent postural instability, falls in the first year of onset, and other features of possible PSP, as follows:

  • Symmetric proximal greater than distal akinesia or rigidity
  • Abnormal neck posture, especially retrocollis
  • Poor or absent response of parkinsonism to levodopa therapy
  • Early dysphagia and dysarthria
  • Early cognitive impairment with at least 2 of the following: apathy, abstract thought impairment, decreased verbal fluency, imitation behavior, or frontal release signs

Criteria for definite PSP are as follows:

  • History of probable or possible PSP and histopathologic evidence that is typical of the disease
  • The proposed criteria for possible PSP are highly sensitive, while the criteria for probable PSP are highly specific, rendering each useful for different analyses and studies. These attempts at clinical diagnosis will hopefully be supplanted by a reliable and objective diagnostic test in the future.
  • The presence of prominent cerebellar signs, hallucinations or dysautonomia in the absence of drug effect, early cortical dementia features, or unilateral dystonia casts doubt on the diagnosis of PSP and should prompt consideration of other neurodegenerative conditions.


Few epidemiologic studies are available to investigate PSP associations. Golbe and coworkers [14] performed a questionnaire survey on a cohort of 75 patients with PSP and matched controls. Surveyed exposures included hydrocarbons, pesticides and herbicides, urban/rural living, occupation, trauma, education level, maternal age, and family history of neurologic diseases. Patients with PSP were less likely than controls to have completed 12 years of education. The authors speculate that education level may be a marker for more direct risk factors such as early life nutrition or occupational or residency exposure.

The role of heredity in the pathophysiology of PSP remains elusive. Although anecdotal reports exist in the literature of apparent familial PSP, several larger series have not noted this association.

In one case-control questionnaire, a trend toward relatives with parkinsonism was reported. Tetrud at al, [43] reported the occurrence of autopsy-proven PSP in a brother-sister pair. Both developed parkinsonism in the eighth decade of life and subsequently exhibited typical features of PSP over the next 5 years. Their mother and, possibly, their maternal grandfather experienced a parkinsonian syndrome, while essential tremor was noted in their father and 2 of the brother’s 3 children. The probands exhibited typical pathologic features of PSP upon autopsy.

Although the current absence of a large kindred with PSP precludes molecular linkage studies, the authors [43] suggest that pairs such as in their report could be pooled for analysis; such occurrences are quite rare.

Although most cases of PSP appear to be sporadic, rare genetically determined forms may exist.

Garcia de Yebenes et al [8] studied a 5-generation family in which PSP was transmitted as an autosomal dominant trait as follows:

  • Two instances of male-to-male transmission were found. The proband had the classic presentation of this disorder beginning with axial rigidity, slowness of movement, and gait difficulty. Over the course of 2 years, he progressed to complete vertical gaze palsy, axial dystonia, retrocollis, and generalized severe akinesia.
  • Postmortem examination demonstrated neurofibrillary tangles (NFTs) and gliosis without prominent senile plaques, the same pathology that was observed in the sporadic cases of PSP described by Steele et al [41].
  • In addition, Garcia de Yebenes et al [8] described 6 other families with multiple affected individuals. These included 2 in which a parent was affected, suggesting autosomal dominant inheritance, and 1 family in which parental consanguinity occurred, suggesting recessive inheritance.

The t (tau) protein is important in maintaining neuronal morphology through microtubule binding. Abnormalities of the t protein have been noted in several neurodegenerative diseases. Under abnormal circumstances, the normally soluble t protein may collect in insoluble protease-resistant helical filaments. The exact triggers for the conversion from normal t to the aggregate form are not completely understood.

  • This model shares some characteristics with prion disease (Creutzfeldt-Jakob disease), in which an abnormal insoluble prion protein (PrP) isoform accumulates.
  • Work by Conrad and colleagues [7] has demonstrated the overrepresentation of the homozygous t A0 allele in patients with PSP compared to controls.
  • Accordingly, the t A0 allele may be a genetic marker of increased susceptibility to the PSP pathophysiology. The t A0 allele status was not required or sufficient to predict the occurrence of PSP.

Although the e4 allele of apoprotein E gene (ApoE) is a significant risk factor for the development of Alzheimer disease and is overrepresented in individuals with Lewy body disease, it is not associated with PSP, Parkinson disease, or alcoholic dementia.


  1. Albers DS, Augood SJ: New insights into progressive supranuclear palsy. Trends Neurosci 2001 Jun; 24(6): 347-53[Medline].
  2. Aldrich MS, Foster NL, White RF, et al: Sleep abnormalities in progressive supranuclear palsy. Ann Neurol 1989 Jun; 25(6): 577-81.
  3. Arnold G, Tatsch K, Oertel WH: Clinical progressive supranuclear palsy: differential diagnosis by IBZM- SPECT and MRI. J Neural Transm Suppl 1994; 42: 111-8.
  4. Barclay CL, Lang AE: Dystonia in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 1997 Apr; 62(4): 352-6.
  5. Blin J, Baron JC, Dubois B, et al: Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations. Arch Neurol 1990 Jul; 47(7): 747-52.
  6. Brooks DJ, Ibanez V, Sawle GV, et al: Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol 1990 Oct; 28(4): 547-55.
  7. Conrad C, Andreadis A, Trojanowski JQ, et al: Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol 1997 Feb; 41(2): 277-81.
  8. de Yebenes JG, Sarasa JL, Daniel SE: Familial progressive supranuclear palsy. Description of a pedigree and review of the literature. Brain 1995 Oct; 118 ( Pt 5): 1095-103.
  9. Drayer BP, Olanow W, Burger P, et al: Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology 1986 May; 159(2): 493-8.
  10. Foster NL, Gilman S, Berent S, et al: Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography. Ann Neurol 1988 Sep; 24(3): 399-406.
  11. Foster NL, Gilman S, Berent S: Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities. J Neurol Neurosurg Psychiatry 1992 Aug; 55(8): 707-13.
  12. Gibb WR, Luthert PJ, Marsden CD: Corticobasal degeneration. Brain 1989 Oct; 112 ( Pt 5): 1171-92.
  13. Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC: Prevalence and natural history of progressive supranuclear palsy. Neurology 1988 Jul; 38(7): 1031-4.
  14. Golbe LI, Rubin RS, Cody RP, et al: Follow-up study of risk factors in progressive supranuclear palsy. Neurology 1996 Jul; 47(1): 148-54.
  15. Golbe LI: Progressive Supranuclear Palsy. Curr Treat Options Neurol 2001 Nov; 3(6): 473-477.
  16. Gross RA, Spehlmann R, Daniels JC: Sleep disturbances in progressive supranuclear palsy. Electroencephalogr Clin Neurophysiol 1978 Jul; 45(1): 16-25.
  17. Hamilton SR: Neuro-ophthalmology of movement disorders. Curr Opin Ophthalmol 2000 Dec; 11(6): 403-7.
  18. Jackson JA, Jankovic J, Ford J: Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol 1983 Mar; 13(3): 273-8.
  19. Jankovic J, Friedman DI, Pirozzolo FJ, McCrary JA: Progressive supranuclear palsy: motor, neurobehavioral, and neuro- ophthalmic findings. Adv Neurol 1990; 53: 293-304.
  20. Kristensen MO: Progressive supranuclear palsy–20 years later. Acta Neurol Scand 1985 Mar; 71(3): 177-89.
  21. Kuniyoshi S, Riley DE, Zee DS: Distinguishing progressive supranuclear palsy from other forms of Parkinson’s disease: evaluation of new signs. Ann N Y Acad Sci 2002 Apr; 956: 484-6.
  22. Laffont F, Autret A, Minz M: [Polygraphic study of nocturnal sleep in three degenerative diseases: ALS, oligo-ponto-cerebellar atrophy, and progressive supranuclear palsy]. Waking Sleeping 1979 Jan; 3(1): 17-30.
  23. Laffont F, Autret A, Minz M, et al: [Polygraphic sleep recordings in 9 cases of Steele-Richardson’s disease (author’s transl)]. Rev Neurol (Paris) 1979 Feb; 135(2): 127-41.
  24. Leigh JR, Zee DS: The neurology of eye movements. 3rd ed. New York, NY: Oxford University Press; 1999: 521-525.
  25. Litvan I, Agid Y, Jankovic J, et al: Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology 1996 Apr; 46(4): 922-30.
  26. Litvan I, Agid Y, Calne D, et al: Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996 Jul; 47(1): 1-9.
  27. Litvan I, Mega MS, Cummings JL, Fairbanks L: Neuropsychiatric aspects of progressive supranuclear palsy. Neurology 1996 Nov; 47(5): 1184-9.
  28. Litvan I, Hauw JJ, Bartko JJ: Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 1996 Jan; 55(1): 97-105.
  29. Litvan I: Diagnosis and management of progressive supranuclear palsy. Semin Neurol 2001; 21(1): 41-8.
  30. Litvan I, Mangone CA, McKee A, et al: Natural history of progressive supranuclear palsy (Steele-Richardson- Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry 1996 Jun; 60(6): 615-20.
  31. Maher ER, Lees AJ: The clinical features and natural history of the Steele-Richardson- Olszewski syndrome (progressive supranuclear palsy). Neurology 1986 Jul; 36(7): 1005-8.
  32. Mark MH: Lumping and splitting the Parkinson Plus syndromes: dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and cortical-basal ganglionic degeneration. Neurol Clin 2001 Aug; 19(3): 607-27, vi.
  33. Mastaglia FL, Grainger K, Kee F, et al: Progressive supranuclear palsy (the Steele-Richardson-Olszewski syndrome) clinical and electrophysiological observations in eleven cases. Proc Aust Assoc Neurol 1973; 10(0): 35-44.
  34. Nath U, Ben-Shlomo Y, Thomson RG: The prevalence of progressive supranuclear palsy (Steele-Richardson- Olszewski syndrome) in the UK. Brain 2001 Jul; 124(Pt 7): 1438-49.
  35. Polo KB, Jabbari B: Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Neurol 1994 Feb; 35(2): 237-9.
  36. Rafal RD, Friedman JH: Limb dystonia in progressive supranuclear palsy. Neurology 1987 Sep; 37(9): 1546-9.
  37. Sakakibara R, Hattori T, Tojo M, et al: Micturitional disturbance in progressive supranuclear palsy. J Auton Nerv Syst 1993 Nov; 45(2): 101-6.
  38. Santamaria J, Iranzo A: Alteraciones del sueno en los trastornos del movimiento. Neurologia 1997; 12 (Suppl 3): 35-47.
  39. Savoiardo M, Girotti F, Strada L, Ciceri E: Magnetic resonance imaging in progressive supranuclear palsy and other parkinsonian disorders. J Neural Transm Suppl 1994; 42: 93-110.
  40. Schonfeld SM, Golbe LI, Sage JI, et al: Computed tomographic findings in progressive supranuclear palsy: correlation with clinical grade. Mov Disord 1987; 2(4): 263-78.
  41. Steele JC, Richardson JC, Olszewski J: Progressive supranuclear palsy. Arch Neurol 1964; 10: 333-359.
  42. Stern MB, Braffman BH, Skolnick BE, et al: Magnetic resonance imaging in Parkinson’s disease and parkinsonian syndromes. Neurology 1989 Nov; 39(11): 1524-6.
  43. Tetrud JW, Golbe LI, Forno LS, Farmer PM: Autopsy-proven progressive supranuclear palsy in two siblings. Neurology 1996 Apr; 46(4): 931-4.
  44. Tolosa E, Espuna M, Valls J: Bladder dysfunction in PSP and other parkinsonian disorders. Mov Disord 1997; 12: 272.
  45. Tolosa E, Valldeoriola F: Progressive supranuclear palsy. In: Jankovic J, Tolosa E, eds. Parkinson’s Disease and Movement Disorders. 3rd ed. Baltimore, Md: William & Wilkins; 1998: 221-243.
  46. Warmuth-Metz M, Naumann M, Csoti I: Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol 2001 Jul; 58(7): 1076-9.
  47. Kraft E, Schwarz J, Trenkwalder C, et al. The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy?. Arch Neurol. 1999;56(2):225–228.
  48. Kato N, Arai K, Hattori T. Study of the rostral midbrain atrophy in progressive supranuclear palsy. J Neurol Sci. 2003;210(1–2):57–60.
  49. Oba H, Yagishita A, Terada H, et al. New and reliable MRI diagnosis for progressive supranuclear palsy. Neurology. 2005;64(12):2050–2055.
  50. Warmuth-Metz M, Naumann M, Csoti I, et al. Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy. Arch Neurol. 2001;58(7):1076–1079.
  51. Paviour DC, Price SL, Stevens JM, et al. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology. 2005;64(4):675–679.
  52. Davie CA, Barker GJ, Machado C, et al. Proton magnetic resonance spectroscopy in Steele-Richardson-Olszewski syndrome. Mov Disord. 1997;12(5):767–771.
Case record: A case with multiple system atrophy (MSA)
Dec 7th, 2009 by Administrator

The author: Professor Yasser Metwally


December 7, 2009 —  A case with multiple system atrophy (MSA)

  • Clinical picture

A 54-year-old engineer developed erectile dysfunction followed a year later by progressive clumsiness and slurred speech. Over the following year, he became increasingly unsteady on his feet and frequently spilled drinks because of clumsiness of his hands. Over the next 2 years his movements became slow and he complained of stiffness and light headedness and episodes of urinary retention required self-catheterization. His motor symptoms transiently and partially improved with L-dopa but he experienced orofacial dystonia while taking the medication. There was no relevant family history and he never drank alcohol excessively. Examination revealed normal cognition, jerky pursuit and dysmetric saccadic eye movements, anterocollis, orofacial dystonia, and truncal ataxia. Routine blood tests, thyroid function tests, vitamin E level, autoantibodies screen, and genetic tests for spinocerebellar ataxia 1 to 3, 6, and 7 and Friedreich ataxia were either normal or negative. Autonomic function test showed marked cardiovascular autonomic failure with orthostatic hypotension.

This patient presented with atypical parkinsonism with early autonomic dysfunction and cerebellar signs. This is the classical presentation of MSA that usually manifests in middle age and progresses relentlessly with a mean survival of 6 to 9 years. [1] Initial L-dopa response occurs in a third of patients, however 90% of them are unresponsive on long-term follow-up. Orofacial dystonia is a feature observed in more than half of all MSA patients and may occur spontaneously or more usually as a complication of L-dopa therapy. Disproportionate anterocollis is another characteristic feature seen in MSA. Early urinary incontinence and syncope are characteristic for MSA and contrast with the later autonomic involvement often seen in Parkinson disease (PD). Early erectile dysfunction is also common and urinary retention as occurred in this case can rarely be an early symptom. There are two subtypes of MSA: parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes. Neuropathologically, all subtypes of MSA are collectively characterized by the finding of a-synuclein glial cytoplasmic inclusions in the striatum and cerebellum (GCIs). [2]

The clinical differential diagnoses for this patient would include the following: other atypical parkinsonian syndromes, adult-onset cerebellar ataxia that can be hereditary despite a negative family history (eg, Friedreich ataxia), spinocerebellar ataxia, Fragile X tremor ataxia syndrome (FXTA) syndrome, and autoimmune conditions in association with Anti-GAD in celiac disease, anti-Yo and anti-Hu in paraneoplastic syndromes. Toxic and metabolic conditions (eg, hypothyroidism, alcohol-related cerebellar degeneration) should also be considered, as some of these are potentially reversible.

Neuroimaging is not included in the consensus diagnostic criteria of MSA. [3] Nevertheless, typical neurologic findings can assist in differentiating MSA from other causes of parkinsonism and cerebellar ataixia (Fig. 1,2). [4] The “hot-cross bun” sign observed in this case is characterized by cruciform signal hyperintensity on T2-weighted images in mid pons, which resembles a hot-cross bun, traditionally baked on the last Thursday before Easter (see Fig. 2A). [5] This finding is thought to correspond to the loss of pontine neurons and myelinated transverse cerebellar fibers with preservation of the corticospinal tracts. However, this sign is not specific to MSA and has been reported in other conditions such as spinocerebellar ataxia (SCA). The more common typical radiological findings in MSA include atrophy of the cerebellum, most prominently in the vermis, middle cerebellar peduncles, pons, and lower brainstem. In addition to putaminal atrophy, a characteristic hypointense signal in T2 with hyperintense rim, corresponding to reactive gliosis and astrogliosis, can be observed in the external putamen, and is termed “slit-like void sign” (see Fig. 2B). [6,7] This combination of hypointense and hyperintense putaminal signal change is specific for MSA and its finding can be used to differentiate MSA from PSP and PD. [7] Hypointensity alone without hyperintense rim is a sensitive radiological feature but nonspecific for MSA. [7,8,9,10]

Click to enlarge figure

Figure 1.  A hot cross bun, or cross-bun, is a type of sweet spiced bun made with currants or raisins and leavened with yeast. It has a cross marked on the top which might be effected in one of a variety of ways including: pastry, flour and water mixture, rice paper, icing, or intersecting cuts. (Click to enlarge figure)

Click to enlarge figure

Figure 2. (A) Axial T2-weighted MR imaging demonstrates cruciform hyperintense signal changes in mid pons, the so-called “hot-cross bun sign.” (B) Axial T2-weighted MR imaging demonstrates hypointensity in association with hyperintense rim in the external putamen, which is termed “slit-like void sign.” (Click to enlarge figure)

  • Discussion

Multiple system atrophy most commonly begins in the early 50s and, unlike Parkinson’s disease, it shortens life considerably, with a median survival of 9.3 years.[17] However, there is a wide range both for age at onset and for survival. Parkinsonism occurs in 90% of patients with multiple system atrophy and is usually symmetrical unlike IPD.[17] Cerebellar or pyramidal signs each occur in about half of the patients.[17] Rest tremor is seen in MSA but is far less frequent than in IPD.[17] Further limb ataxia or intention tremor can be present in MSA, particularly in later stages, which is never seen in IPD. [17]

Autonomic dysfunction failure occurs in virtually all patients and it may precede the motor disturbance by months or even some years.[17] In men, impotence is often the first symptom and incontinence, more than retention, is common in both sexes.[17] Symptomatic postural hypotension is common and unlike PD occurs early and before dopaminergic therapy is instituted.[17] Respiratory stridor affects about 30% of patients at some stage and when combined with parkinsonism is highly suggestive of multiple system atrophy.[17] Severe apnoeic attacks and hypoventilation can become severe enough to warrant a tracheostomy.[17] Speech may differ qualitatively from the hypophonic monotony of Parkinson’s disease, incorporating quivering, strained or slurring components.[17] Many patients develop severe aphonia, anarthria and dysphagia, which are rare in Parkinson’s disease.[17]

Unlike PD extraocular smooth pursuit movements are hypometric to pursuit with saccadic intrusion and may also show sustained nystagmus.[17] Square wave jerks may also be evident on central fixation. Voluntary saccades are usually full and supranuclear gaze problems are noted occasionally.[11,17]

Hyper reflexia in conjunction with spasticity and a positive Babinski response is only seen in MSA and not IPD.[13]

The flexed posture of MSA patients can be extreme and unlike patients of IPD they become bent double with their chins on their chest.[11,17] Limb dystonia can also be a feature of MSA.

While frontal executive problems are found in MSA, frank dementiais are rare, as are the hallucinations, confusion and psychosis associated with cortical Lewy body disease.[11]

MSA patients show a poor levodopa response. However, it can be good or excellent in 25% of patients, but this is usually transient.[11,17] Still levodopa responses cannot be used to exclude a diagnosis of MSA. Levodopa induced dyskinesias in multiple system atrophy maybe absent or, when present, take the form of predominantly dystonic movements affecting the face and neck more than the limbs.[11,17]

Autonomic function tests can document disturbed control of blood pressure and heart rate, but taken in isolation they are not particularly helpful in determining whether this is due to multiple system atrophy or due to Parkinson’s disease, as similar results can be obtained in both diseases.[17] In contrast, an abnormal external sphincter electromyogram reflecting loss of anterior horn cells in Onuf’s nucleus in the sacral cord is highly suggestive of multiple system atrophy in the appropriate clinical setting. The presence of putaminal hypo intensity relative to globus pallidus on 1.5 tesla T2 weighted MRI or slit hyper intensity of the lateral putaminal margin, with or without cerebellar and putaminal atrophy may suggest MSA.[1,17] In a study MRI showed, a hyper intense rim at the lateral edge of the dorsolateral putamen in 34.5% of cases and a ‘hot cross bun’ sign in the pontine basis (PB) in 63.3%.[5,7] However neuro imaging may entirely be normal. It is useful to remember that a non-demented patient who is impotent and incontinent with poorly responsive parkinsonism, pyramidal and cerebellar signs does not have another single alternative diagnosis.


  1. Bhidayasiri R, Ling H. Multiple system atrophy. Neurologist. 2008;14(4):224–237.
  2. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989;94(1–3):79–100.
  3. Gilman S, Low PA, Quinn N, et al. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci. 1999;163(1):94–98.
  4. Schrag A, Good CD, Miszkiel K, et al. Differentiation of a typical parkinsonian syndromes with routine MRI. Neurology. 2000;54(3):697–702.
  5. Schrag A, Kingsley D, Phatouros C, et al. Clinical usefulness of magnetic resonance imaging in multiple system atrophy. J Neurol Neurosurg Psychiatr. 1998;65(1):65–71.
  6. Lang AE, Curran T, Provias J, et al. Striatonigral degeneration: iron deposition in putamen correlates with the slit-like void signal of magnetic resonance imaging. Can J Neurol Sci. 1994;21(4):311–318.
  7. Kraft E, Schwarz J, Trenkwalder C, et al. The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy?. Arch Neurol. 1999;56(2):225–228.
  8. Multiple System Atrophy (MSA) [Full text]
  9. Neuroimaging of idiopathic parkinson disease [Full text]
  10. The idiopathic parkinson disease: A magnetic resonance imaging study with correlation of the clinical picture and the pattern of levodopa responsiveness. Metwally, MYM (2000): Ain Shams medical journal, VOL 51, No 1,2,3, pp 181-198 [PDF]
  11. Metwally, MYM: Textbook of neuroimaging, A CD-ROM publication, (Metwally, MYM editor) WEB-CD agency for electronic publication, version 9.4a October 2009 [Click to have a look at the home page]
  12. Conventional MR Imaging (cMR) of Parkinson disease and Parkinsonian syndromes [Full text]
  13. Cortical Basal Ganglionic Degeneration [Full text]
  14. Progressive Supranuclear Palsy and Corticobasal Degeneration: Similarities and Differences [Full text]
  15. Tau and tauopathy [Full text]
  16. Parkinson-plus syndromes [Full text]
  17. The akinetic-rigid syndromes [Full text]

»  Substance:WordPress   »  Style:Ahren Ahimsa
© Copyright Yasser Metwally, All rights reserved