Pisa syndrome as presenting symptom of amyotrophic lateral sclerosis

Pisa syndrome (PS) is a truncal dystonia causing lateral flexion of the body. It was first described by Ekbom [1] as a side effect of neuroleptic drugs. It has been reported as a drug-induced syndrome secondary to neuroleptics, antidepressants, antiemetics, cholinesterase inhibitors and dopaminagonists. It was associated with some neurodegenerative diseases including Alzheimer’s dementia, multiple system atrophy, Parkinson’s disease (PD), and it was also reported as an idiopathic form [2–6]. We describe the clinical features of a patient affected by PD, who developed PS as presenting symptom of amyotrophic lateral sclerosis (ALS). A 63 year-old man had suffered from PD, starting with a 6 Hz left-hand rest tremor, since his mid-50s. PD diagnosis was made according to the UK PD Society Brain Bank criteria [7] and supported by a ‘‘typical’’ I-FP-CIT SPECT (Fig. 1). The parkinsonian symptoms had progressed slowly and the patient had received levodopa therapy with sustained benefits for almost 10 years. Because of motor fluctuations, his physician decided to switch levodopa/benserazide (LB) 600/150 mg daily to levodopa/carbidopa/entacapone (LCE) 600/150/1,200 mg daily. Two weeks later, he complained of leaning forward to the left side, which was prominent when walking or sitting, and was relieved when lying back on his left side. Based on the temporal relation with the therapeutic change, LCE-induced PS was suspected. The treatment was switched to LB (600/150 mg daily) with PS transient and incomplete improvement. Six months later he was referred to our department for a second opinion about his abnormal posture which became fixed and unrelated to his motor state. Over the past several months, he had also displayed progressive weakness and had become wheelchair dependent without any history of pain, sensory loss or trauma. On examination, wasting and fasciculations were prominent in all muscles below his knees. Strength testing showed a bilateral footdrop. Deep tendon reflexes were brisk in both lower and upper limbs with bilateral extensor plantar response. Mental status, cranial nerves function and sensory examination were normal. The marked left truncal flexion, diagnosed as PS, was persistent in both on and off state (Fig. 2) and unresponsive to any therapeutic changes. On EMG evaluation, there was evidence of widespread spontaneous activity in proximal and distal muscles of all four limbs, with positive sharp waves and fibrillation potentials more prominent in the distal lower extremities. Bulbar muscles were normal; bilateral thoracic paraspinal muscles, at T6–T8 levels, showed profuse fibrillation potentials and positive sharp waves, mainly in the left side. All the muscles sampled in the upper, lower extremities and thoracic paraspinal, showed large-amplitude, longduration, polyphasic motor unit action potentials with decreased recruitment. Fasciculations were evident in the lower limbs but not in paraspinal muscles. Brain and cervicodorsolumbar spine MRI, serological and liquoral exams were unrevealing. Clinical and EMG findings were consistent with diagnosis of ALS according to El Escorial Criteria [8]. The patient died almost 1 year after ALS diagnosis because of respiratory insufficiency. M. Deriu and D. Murgia equally contributed to the paper.