Dear Editor,

Subacute sclerosing panencephalitis (SSPE) is a slowly progressive central nervous system disorder affecting children and young individuals and is caused by mutant measles virus persistence. Patients with SSPE may present with extrapyramidal manifestations such as tics, dystonia, parkinsonism, and chorea [1]. Here, we report the case of a patient with SSPE with Pisa syndrome, a disorder of postural abnormality with lateral flexion of the trunk.

A 23-year-old man presented with recurrent falls, a decline in scholastic performance, personality changes, and jerky movements of the body, especially the right upper limb, for the last 8–9 months. For the last 1 month, the patient also had a rightsided tilt of the body in sitting and/or standing positions, with the tendency to fall to the right side. The tilt was not present while lying or on passive mobilization, suggesting Pisa syndrome (Figure 1A, Supplementary Video 1 in the online-only Data Supplement).

Initially, he had recurrent falls and therefore suffered many injuries to his face. This was followed by behavioral changes such as pathological laughing. His scholastic performance also deteriorated over time. Subsequently, he developed slowness in all body movements and drooling of saliva. Sometimes, he would suddenly start walking very fast and could not balance himself. He experienced intermittent involuntary and brief jerky movements of the right upper limb, head, and trunk. There was no history of fever, headache, or any psychiatric illness preceding the current illness. Perinatal history and developmental history were normal. There was no history of measles in childhood. The status of measles vaccination was unknown due to poor record-keeping. No significant family history related to the current disease was present. No history of cholinesterase inhibitor, neuroleptic, or tricyclic antidepressant intake was present.

On examination, the patient was conscious, obeyed commands and had normal vital signs. Pathological laughter was present. Multiple injury marks were present on his face. The Mini-Mental Status Examination score was 14/30. The glabellar tap sign was positive with a blink rate of 8–9 per minute. Other frontal release signs were absent. He had slow saccades with the full range of all ocular movements. No Kayser Fleischer ring was seen. Myoclonic jerks of the right upper limb, head, and trunk were noted. Bradykinesia in the right upper limb was seen, along with evidence of slowed finger taps and mild cogwheel rigidity at the wrist. Lateral bending of the trunk toward the right side suggesting Pisa syndrome was present, with the tendency to fall to the right side. This bending subsided when the patient was in the lying position and reappeared when in the standing or sitting position, with no deformity noted in spine examination. Gait was festinating and interrupted by falls due to axial myoclonic jerks. No cerebellar signs were present.

The results of a complete blood count, liver function tests, and renal function tests were normal. The thyroid profile and serum ceruloplasmin level were normal. Test results for anti-nuclear antibodies and anti-thyroid peroxidase antibodies were negative. Electroencephalography (EEG) revealed a normal background interrupted with bilateral, synchronous, high voltage delta waves recurring at an interval of 4–6 seconds (Figure 1C). Cerebrospinal fluid (CSF) analysis revealed 3 total cells (100% lymphocytes), with 61.4 mg/dL protein and 75 mg/dL glucose. CSF autoimmune encephalitis and neurotrophic panels, including tests for flavivirus, enterovirus, paramyxovirus and herpes virus, were negative. CSF measles immunoglobulin G (IgG) antibody levels were very high (> 300 AU/mL), suggestive of a past measles infection. Brain magnetic resonance imaging (MRI) showed subtle diffuse symmetrical T2/FLAIR hyperintensities in the periventricular and deep white matter of the bilateral frontoparietal region, including the centrum semiovale, with diffuse cerebral atrophy (Figure 1B). Genetic testing for host susceptibility was not performed.

In view of the clinical presentation of new-onset deficits in cognitive function, myoclonic jerks and falls, characteristic EEG and brain MRI findings, and high CSF measles IgG antibody levels, the possibility of SSPE was considered, although a history of measles infection was not present.

The patient was started on oral sodium valproate 300 mg twice daily, clonazepam 0.25 mg three times daily and glycopyrrolate 0.5 mg twice daily. He showed mild improvement in Pisa syndrome and a reduction in myoclonic jerks and falls. Intrathecal interferon therapy was offered, but it was refused by the patient’s relatives due to financial constraints.

Pisa syndrome is a unique disorder associated with postural abnormalities named after the leaning tower of Pisa [2]. It was first described in 1972 by Ekbom and colleagues as an adverse effect of haloperidol leading to lateral truncal flexion in the standing position due to axial dystonia [3]. It is mostly reversible in acute or subacute cases and is most commonly associated with neurodegenerative disorders (Parkinson’s disease, multiple system atrophy) or drugs such as neuroleptics, tricyclic antidepressants, antiemetics and anticholinesterases [4].

In the abovementioned case, Pisa syndrome was noticed in a patient with SSPE. To our knowledge, only two cases of Pisa syndrome in patients with SSPE have been reported in the literature. The first case was described by Malhotra et al. [5] in a 23-year-old man. Pandey et al. [6] described the second case of Pisa syndrome in an 8-year-old child with SSPE. The patients had similar complaints, such as cognitive decline, behavioral changes, recurrent falls, and body tilt to the right. In the patients whose cases were reported by Pandey et al. [6] and Malhotra et al. [5], a history of measles in the past was present, whereas in our patient, there was no such history. Both of these patients were unvaccinated for measles.

In the case reported by Malhotra et al. [5], the patient’s brain MRI findings were similar to those of our patient, showing subcortical white matter hyperintensities involving the frontal, parietal, and occipital regions on T2-weighted and fluid-attenuated inversion recovery sequences. However, in the patient whose case was described by Pandey et al. [6], brain MRI showed only right temporo-occipital hyperintensities.

The plausible pathophysiology of Pisa syndrome is the imbalance between dopaminergic and cholinergic neurotransmission, as suggested by the response to anticholinergics and a reduction in or withdrawal of neuroleptics [7,8]. However, the exact mechanism remains unknown. Additionally, the pathophysiology behind the appearance of Pisa syndrome in these patients with SSPE is not clear.

This case is the third case of Pisa syndrome reported in a patient with SSPE. Therefore, we can conclude that Pisa syndrome is an uncommon presentation of SSPE and should be considered in young patients with the combination of parkinsonism, myoclonic jerks, and cognitive decline.

Supplementary Material

Video 1.

Video of the patient showing lateral bending toward the right side, abnormal gait with a tendency to fall, and right upper limb recurrent myoclonic jerks.

Notes

Ethics Statement

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Fortis Hospital Mohali research ethics committee and with the 2013 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all the patients included in the study.

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Author contributions

Conceptualization: all authors. Data curation: Sandeep Kaur, Amit Shankar Singh. Formal analysis: Sandeep Kaur, Amit Shankar Singh, Jeenendra Prakash Singhvi, Sudesh Prabhakar, Arun Kaul. Investigation: all authors. Methodology: Sandeep Kaur, Amit Shankar Singh, Jeenendra Prakash Singhvi, Sudesh Prabhakar, Arun Kaul. Project administration: Sandeep Kaur, Amit Shankar Singh, Sudesh Prabhakar, Harpreet Singh Mann. Resources: Sandeep Kaur, Amit Shankar Singh, Jeenendra Prakash Singhvi, Sudesh Prabhakar, Harpreet Singh Mann. Supervision: Jeenendra Prakash Singhvi, Sudesh Prabhakar, Arun kaul, Harpreet Singh Mann. Validation: Sandeep Kaur, Amit Shankar Singh, Jeenendra Prakash Singhvi, Sudesh Prabhakar, Arun Kaul, Harpreet Singh Mann. Visualization: all authors. Writing—original draft: all authors. Writing—review & editing: all authors.

Figure 1.

Image of patient with Pisa syndrome with magnetic resonance imaging (MRI) brain and electroencephalogram. A: Image of the patient showing lateral bending of the trunk toward the right side. B: Brain MRI showed subtle diffuse symmetrical T2/fluid-attenuated inversion recovery hyperintensities in the periventricular and deep white matter of the bilateral frontoparietal region, including the centrum semiovale, with diffuse cerebral atrophy. C: Electroencephalography revealed a normal background interrupted with bilateral, synchronous, high voltage delta waves recurring at an interval of 4–6 seconds.

REFERENCES

• 1. Prashanth LK, Taly AB, Ravi V, Sinha S, Arunodaya GR. Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre. J Neurol Neurosurg Psychiatry 2006;77:630–633.ArticlePubMedPMC
• 2. Doherty KM, Davagnanam I, Molloy S, Silveira-Moriyama L, Lees AJ. Pisa syndrome in Parkinson’s disease: a mobile or fixed deformity? J Neurol Neurosurg Psychiatry 2013;84:1400–1403.ArticlePubMedPMC
• 3. Ekbom K, Lindholm H, Ljungberg L. New dystonic syndrome associated with butyrophenone therapy. Z Neurol 1972;202:94–103.ArticlePubMedPDF
• 4. Barone P, Santangelo G, Amboni M, Pellecchia MT, Vitale C. Pisa syndrome in Parkinson’s disease and parkinsonism: clinical features, pathophysiology, and treatment. Lancet Neurol 2016;15:1063–1074.ArticlePubMed
• 5. Malhotra HS, Garg RK. Pearls & Oy-sters: Pisa syndrome: an unusual feature of adult-onset fulminant SSPE. Neurology 2015;84:e12–e14.ArticlePubMed
• 6. Pandey S, Tomar LR, Tater P. Pisa syndrome in a child with subacute sclerosing panencephalitis. JAMA Neurol 2018;75:255–256.ArticlePubMed
• 7. Villarejo A, Camacho A, García–Ramos R, Moreno T, Penas M, Juntas R, et al. Cholinergic–dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol 2003;26:119–121.ArticlePubMed
• 8. Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus). CNS Drugs 2002;16:165–174.ArticlePubMed

Figure & Data

References

Citations

Citations to this article as recorded by  

• Movement Disorders in Patients with Subacute Sclerosing Panencephalitis: A Systematic Review
  Divyani Garg, Sahil Patel, Charulata S. Sankhla, Vikram V. Holla, Vijayashankar Paramanandam, Prashanth L. Kukkle, Sanjay Pandey, Susanne A. Schneider, Pramod K. Pal
  Movement Disorders Clinical Practice.2024; 11(7): 770.     CrossRef

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