"Hot cross bun" sign is a valuable MRI finding in multiple system atrophy

M.A. ARAMI

CONSULTANT NEUROLOGIST**, ** Department of Neurology , Milad Hospital, Tehran, Iran.

Y. KHOLGHI

CONSULTANT NEUROLOGY*, *Department of Neurology , Loghman Hospital, Shahid Beheshti University of Medicine, Tehran, Iran

Abstract:

Multiple system atrophy (MSA) is a degenerative disorder of central nervous system. A definite diagnosis is only possible at necropsy when cell loss and gliosis as well as glial cytoplasmic inclusions are found in pathologic examination. Clinically, diagnosis of MSA especially in early stages is often difficult and differentiation from idiopathic Parkinson's disease may results a high rate of misdiagnosis. Here we report two cases of multiple system atrophy in which we found a valuable neuroimaging sign, “hot cross bun”.

Introduction:

Multiple system atrophy (MSA) is a term suggested by Graham and Oppenheimer in1969 as a description of a group of patients with a disorder of unknown cause affecting extrapyramidal, pyramidal, cerebellar and autonomic pathways. MSA included the disorders were called Striatonigral Degeneration, Olivopontocerebellar atrophy (OPCA), and the Shy-Dragger syndrome. The clinical syndrome can include various combinations of symptoms of autonomic dysfunction as well as additional symptoms such as rigidity, tremor and loss of associated movements. It usually develops over five years.

Brain MRI often shows abnormalities of the basal ganglia or brain stem which help to differentiate between multiple system atrophy and idiopathic Parkinson's disease. (1, 2, 3) Hypointensity of the putamen, especially in the posterior and lateral part, which equals or exceeds that of the globus pallidus on T2 weighted images on MRI, was first described in atypical and poorly levodopa responsive parkinsonism.(4) However considerable overlap has been reported between individual patients with multiple system atrophy, idiopathic Parkinson's disease, and control patients.(5)

Here we report two cases having features of degeneration of cerebellar, extrapyramidal, pyramidal, and autonomic nervous systems which initially presented as urinary dysfunction and Parkinsonism.

Presentation of Cases:

Case 1

A 53-year-old man was evaluated in our neurology clinic because of difficulty in walking (progressive recurrent falling with unsteady gait) and symptoms of orthostatic hypotension. The patient had been well until 5 years earlier; when he began to fall occasionally (This was not vertigo or seizure activity). He also had constipation and urinary symptoms as frequency and incontinence in early stage of disease. He had mild tremor in both hands that subside 1-2 years later.

During the past 3 years, the falls and occasional episodes of urinary incontinence became more frequent. He has suffered erectile dysfunction (impotency) since1-2 years ago and was referred to a clinic at this hospital that specializes in Parkinson's disease and movement disorders.

There was no history of hypertension, diabetes, stroke-like episodes, headache, and trauma, infections of the central nervous system, exposure to neurotoxic agents and use of drugs with nervous system side effects.

The general physical examination revealed no abnormalities except orthostatic hypotension (orthostatic fall in blood pressure by >30 mm Hg systolic). Neurological examination revealed an alert, oriented, attentive man. He had mild hypophonia, mild-to-moderate dysarthria but without paraphasic errors. The patient's cranial-nerve functions were intact. The eye movements were full. There was no nystagmus. His face had a masking expression and a reduced blinking rate. The tone was increased in all limbs ( plus cogwheel rigidity). There were bilateral cerebellar signs as evidenced by abnormal finger to nose test, knee heel test, dysdiadokokinesia and cerebellar type of speech.

The deep-tendon reflexes were symmetrically increased in the four limbs. He rise slowly from a chair, and both bradykinesia and truncal ataxia were evident. He walked stiffly and with a widened stance. Testing for sensation revealed normal results. He had a sustained blink response to finger tapping on his forehead (Myerson sign) and an increased jaw reflex.

A trial of carbidopa (50 mg)–levodopa (200 mg), taken orally four times per day was begun without any benefits even with increasing dose in early stage of disease. An MRI study showed the “hot cross bun” sign. (Fig 1)

Position for fig 1- Hot Cross Bun sign in case 1

Case 2

A 50 year old man referred our hospital for evaluation of “a patient with drug resistant Parkinson disease”. He has history of hesitancy and stress incontinence, prolonged constipation and impotency with recurrent falling in combination with progressive stiffening of limbs and body since 5 years prior to admission. With progression of disease course he had progressive difficulty in walking and since 2 years prior to admission he developed marked increase of rigidity of trunk and limbs. He was not able to work and had disturbance in his professional life. He has also developed stooped position and low mimic face with inappropriate laughing and crying. He can not stand and walk without assistance since 1 years prior to admission. He did not have any limbs weakness or sensory symptoms.

He was not diabetic or hypertensive. His symptoms had progressively increased over past 2 years despite treatment with levodopa-carbidopa, Amantadine and Selegilin in enough doses.

On examination there was infrequent blinking and he had a masked face. He was mentally cooperative and his memory and alertness were good. Cranial nerve examinations showed a brisk jaw jerk but no disturbance in eye movements. There was cogwheel rigidity in the limbs with a full extremities power. Plantar reflex was extensor bilaterally. We were not able to perform cerebellar tests because of marked rigidity in limbs.

Autonomic nervous system showed dysfunction in the form of postural hypotension (diastolic pressure fall more than 15 mm Hg) and persistent urinary incontinence that need Folly catheterization. His MRI study showed typical “hot cross bun” sign. (Fig 2)

Patients are on follow up in our Neurology clinic.

Position for fig 2- Hot Cross Bun sign in case 2

Discussion:

Diagnosis of multiple system atrophy is extremely difficult in early stages of the disease. Wenning et al analyzed the clinical features of 203 cases of pathologically proven MSA. Most patients showed symptoms in their early fifties, with men more commonly affected than women. Seventy four percent of patients suffered some degree of autonomic failure. Parkinsonism was the most common motor disorder (87%), followed by cerebellar ataxia (54%) and pyramidal signs (49%). Severe dementia was not common. Incidence is about 4 per 100,000. Life expectancy is about 7.5 years. (6)

The diagnosis of Multi System Atrophy during life is based on clinical features and thus it is only made with possibility or probability. Definite diagnosis requires pathologic study and demonstration of glial cytoplasmic inclusions and absence of Lewy bodies.

Brain MRI is an important mean of the investigation of patients with unusual parkinsonian syndromes. In patients with MSA, MRI of the brain can detect abnormalities of striatum, cerebellum and brainstem. However, in up to 20% of MSA patients, MRI of the brain is normal. PET scanning may also be helpful. Schrag et al. with a study on 44 patients with multiple system atrophy, 47 patients with idiopathic Parkinson's disease, and 45 controls showed that infratentorial abnormalities occurred significantly more often in patients with multiple system atrophy than other 2 group. They found that infratentorial signal changes have characteristic appearances as pontine hyperintensity that was cruciform resembling a "hot cross bun", whereas those of the middle cerebellar peduncles and the cerebellar hemispheres were diffuse. (7)

Using T2 weighted MRI, Savoiardo et al described hyperintensities in the pons, middle cerebellar peduncles, and cerebellum, corresponding to pontocerebellar tract atrophy, among a mixed group of patients with olivopontocerebellar atrophy including patients with multiple system atrophy.(2) Schulz et al also reported hyperintensities in the pons and middle cerebellar peduncles in patients with multiple system atrophy as well as atrophy of the middle cerebellar peduncles, brainstem, and cerebellum, which were not seen in their patients with idiopathic Parkinson's disease. (3)

The "hot cross bun" appearance in multiple system atrophy is due to loss of pontine neurons and myelinated transverse pontocerebellar fibres with preservation of the corticospinal tracts (7). The "hot cross bun" sign is a radiological sign which has been said to be highly specific for multiple system atrophy (8). However, the specificity and sensitivity of these putaminal and infratentorial abnormalities on routine MRI are unknown. For example Muqit et al. reported a patient with the "hot cross bun" sign who presented with Parkinsonism secondary to presumed vasculitis.

Our patients presented with a severe parkinsonian syndrome associated with cerebellar and urinary incontinence with orthostatic hypotension. According diagnostic criteria both patients are probable cases of multiple system atrophy and both had typical "hot cross bun" sign in their MRI imaging. Although, no other disease than MSA can explain the clinical setting of our patients, but definition of affliction of our patient with MSA needs future following up and finally biopsy. A specific clinical setting in combination of neuroimaging findings were our causes for pertains of MSA diagnose for these patient, that is parkinsonism with marked autonomic symptom and signs and "hot cross bun" sign in MRI.

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