Antineuronal antibody screening in early onset-cognitive decline

Encephalomyelitis with rigidity accompanied by a severe progressive course was first described 40 years ago (Whiteley et al., 1976), although the glycine receptor antibody was only recently identified (Hutchinson et al., 2008) and its consideration in clinical psychiatric practice is in its infancy. Specific screening for glycine receptor antibodies rarely occurs in psychiatry patients, although it is now recommended patients with first episode psychosis are screened for better-known anti-neuronal antibodies (Galletly et al., 2016). Autoimmune encephalitides present with atypical neuropsychiatric manifestations and are at risk of being misdiagnosed as functional psychiatric disorders. A cohort of 52 patients with anti-glycine receptor encephalitis (Carvajal-González et al., 2014) reported 11% had an insidious onset and 1 patient had slowly progressive cognitive impairment. This type of encephalitis has an age range of 1–75 years with hyperekplexia (exaggerated startle) being a peculiar common feature (Carvajal-González et al., 2014). This case report raises the possibility of anti-glycine receptor encephalitis mediating a prolonged history of mood disturbance, persisting orofacial tic and early onset-cognitive decline.

A 54-year-old woman presented to hospital after a 6-week progressive history of decreased movement, 20 kg weight loss and aboulia. Frontotemporal lobe dementia was diagnosed at 49 years following slowly progressive cognitive decline as assessed by her neurologist. At 31, she had developed a persistent orofacial tic which had commenced after a trial of lithium for bipolar affective disorder. The tic had not resolved with lithium cessation.

Examination revealed immobility, with slide sheets for turning and hoist requirement for transfers, a downward gaze and an orolinguofacial tic at a frequency of approximately 7 seconds concurrent with incomprehensible grunting vocalizations. There was infrequent eye contact with a vacant stare and no response to verbal commands. Also evident was low muscle tone, brisk reflexes without clonus, a primitive palmar grip reflex and an upgoing plantar response.

Investigations revealed a low white cell count, lymphopenia, neutropenia, elevated C-Reactive protein, reactive Epstein-Barr virus immunoglobulin serology, raised anti-thyroid peroxidase and positive glycine receptor antibodies. Influenza B was detected on nasopharyngeal swab followed by days of fever. Electroencephalography showed symmetric background low-voltage theta-wave activity. A full body fluorodeoxyglucose-positron emission tomography ruled out paraneoplastic syndrome.

Treatment for anti-glycine receptor encephalitis involved methylprednisolone, intravenous immunoglobulins and rituximab. She also received baclofen for emergence of increased muscle tone and lorazepam for agitation with good effect. Although there were gradual clinical improvements after two courses of immunotherapy with improved eye contact, and tracking of surrounding activities, grunt-like vocalizations persisted, as did unresponsiveness to commands.

Although autoimmune encephalitis was only manifest late in this patient’s presentation, it is unclear if this same autoimmune illness was responsible for the patient’s history of orofacial tics accompanying purported bipolar disorder. In the reported case, while it is possible the anti-glycine receptor encephalitis occurred independent of the premorbid dementia and bipolar disorder, it is also plausible that these presentations were mediated by an autoimmune syndrome with an indolent course of mood symptoms, involuntary movements, cognitive decline and rapid deterioration in the later stages. This case raises the question regarding testing for autoimmune encephalitides in patients with early onset-cognitive decline. We recommend psychiatrists to judiciously screen patients who have atypical neuropsychiatric features, especially marked cognitive decline and unusual motor symptoms for autoimmune encephalitides.