Progressive encephalomyelitis with rigidity and myoclonus

Progressive encephalomyelitis with rigidity and myoclonus (PERM), also known as stiff person syndrome plus (SPS-plus), is a very rare debilitating neurological condition, similar to stiff person syndrome, most often associated with anti-glycine receptor antibodies (anti-GlyR).

Epidemiology

Cases of progressive encephalomyelitis with rigidity and myoclonus (PERM) are limited to case reports and short case series ^1,2. The age of onset is usually in middle-age (40-60 years) and it may be more common in males ^1,2.

Associations

Most cases are not associated with an underlying tumor ^1,2. In rare cases with a reported tumor, thymoma is the most common association^1,2.

Clinical presentation

The clinical presentation is characterized by subacute ^1-3:

• progressive muscle stiffness predominantly affecting the axial muscles and lower limbs

• painful muscle spasms, often stimulus-sensitive

• myoclonus, spontaneous or stimulus-sensitive (e.g. sensory, auditory)

• hyperekplexia

• brainstem dysfunction, e.g. ophthalmoplegia and diplopia, dysphagia, dysarthria

• behavioral changes and encephalopathy, e.g. irritability, aggression, decreased conscious state

• autonomic dysfunction, e.g. hyperhidrosis, xerostomia, tachycardia, urinary retention

• sensory symptoms

• respiratory failure (uncommon)

Pathology

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is thought to be an autoimmune condition, part of the spectrum of autoimmune encephalitides, although its exact pathogenesis is yet to be fully elucidated. Glycine receptor antibodies (anti-GlyR) are implicated in most cases ^1-3, although a similar syndrome has also been reported with dipeptidyl-peptidase–like protein 6 antibodies (anti-DPPX) ^3,4, although these patients often have significant additional gastrointestinal symptoms ³. Rarely, other autoantibodies may also be present, such as anti-GAD65, anti-VGKC and anti-NMDAR ^1,2,5.

Radiographic features

MRI

Neuroimaging of the brain and spinal cord with MRI is usually normal ^2,3. Rarely, there may be non-specific T2/FLAIR hyperintensities present in the brain, brainstem or spinal cord ^2,3.

Treatment and prognosis

Disease-modifying treatment in the acute phase includes aggressive immunosuppression, often encompassing one or more of intravenous methylprednisolone, intravenous immunoglobulin (IV Ig), and plasma exchange (PLEX) ^1-3. Additionally, symptomatic treatment is often concurrently given, such as benzodiazepines and baclofen ¹.

Despite long-term immunosuppression, patients may relapse ^1,2. In one case series, approximately 10% of patients died ².

History and etymology

Progressive encephalomyelitis with rigidity and myoclonus (PERM) was first described in 1976 ⁶.

Differential diagnosis

• stiff person syndrome

• neuromyotonia (e.g. Isaacs syndrome, Morvan syndrome)

• tetanus

• functional neurological disorder